ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, СОДЕРЖАЩАЯ АНИОННОЕ ЛЕКАРСТВЕННОЕ СРЕДСТВО, И СПОСОБ ЕЕ ПОЛУЧЕНИЯ

Группа изобретений относится к фармацевтической промышленности, в частности к композиции для доставки анионного лекарственного средства, содержащей: анионное лекарственное средство; катионное соединение, выбранное из полиэтиленимина и катионного липида формулы 7 (, где n и m = 0-12 при условии 2≤n+m≤12, a и b = 1-6, Rи Rвыбраны из насыщенных и ненасыщенных Cуглеводородов); амфифильный двухблочный блок-сополимер типа AB, состоящий из гидрофильного блока А, выбранного из монометоксиполиэтиленгликоля и полиалкиленгликоля, и гидрофобного блока В, представляющего собой сложный полиэфир; и по меньшей мере одно соединение формулы 1 (RO-CHZ-[A]-[B]-COOM, где A -COO-CHZ-; B -COO-CHY-; R атом водорода, ацетил, бензоил, деканоил, пальмитоил, метил или этил; Z и Y метил; M – Na, K или Li; n=1-30, m=0-20 при условии n+m=7-50) и формулы 6 (YO-[-C(O)-(CHX)-O-]-C(O)-R-C(O)-[-O-(CHX')-C(O)-]-OZ, где X и X' метил; Y и Z – Na, K или Li; m и n целое число от 0 до 95 при условии 5 Подробнее

КОМПОЗИЦИЯ РАЗРУШАЮЩЕЙСЯ ПОЛИМЕРНОЙ МИЦЕЛЛЫ

Настоящее изобретение относится к химико-фармацевтической промышленности и представляет собой композицию полимерной мицеллы, пригодной для инкапсулирования и подходящего высвобождения лекарственных средств, содержащей блок-сополимеры, которые компонуются радиально и имеют гидрофобный сегмент, направленный внутрь, и гидрофильный сегмент, направленный наружу, при этом в качестве блок-сополимеров содержит блок-сополимер, обладающий сродством к ЛПВП, который содержит гидрофобный сегмент полимерной цепи, образованный из гидрофобного производного аминокислоты, полученного в результате введения в боковую цепь аминокислоты стерольного остатка, и блок-сополимер, обладающий сродством к липопротеину за исключением ЛПВП, который содержит гидрофобный сегмент полимерной цепи, образованный из гидрофобного производного аминокислоты, полученного в результате введения в боковую цепь аминокислоты гидрофобной группы, обладающей линейной или разветвленной структурой. Изобретение обеспечивает стабильное инкапсулирование ...

Cisplatin- und andere Wirkstoffe oder Gene eingekapselt in Liposomen zur menschlichen Krebstherapie

Sterols modified by polyethylene glycol, the preparation and the use thereof

Compositions and methods for organ specific delivery of nucleic acids

Compositions and methods for organ specific delivery of nucleic acids

Self-assembling amphiphillic polymers as antiviral agents

Self-assembling amphiphilic polymers as antiviral agents

Self-assembling amphiphillic polymers as antiviral agents

Self-assembling amphiphilic polymers as anticanceragents

Self-assembling amphiphilic polymers as anticanceragents

Self-assembling amphiphilic polymers as anticanceragents

Self-assembling amphiphilic polymers as anticanceragents

Self-assembling amphiphillic polymers as antiviral agents

TOCOPHEROLMODIFIZIERTE THERAPEUTIC DRUG CONNECTION

HYALURONSÄUREDERIVAT WITH A URETHANE CONNECTION

TARGETING OF THERAPEUTIC MEANS BY USE OF POLYSACCHARIDEN

MATERIALS AND PROCEDURES FOR MANUFACTURING IMPROVED MIZELLENZUSAMMENSETZUNGEN

UNIVERSITY-MOLECULAR POLYMERI MICELLE, THE ONE IONIZABLE CORE CONTAINING

Targeted artificial gene delivery

Polymeric micelles for drug delivery

Integrin targeted imaging agents

Steroid analogs and characterization and treatment methods

Negatively charged amphiphilic block copolymer as drug carrier and complex thereof with positively charged drug

Drug delivery vehicle comprising conjugates between targeting polyamino acids and fatty acids

The invention provide herein provides for a targeted drug delivery vehicle compositions, methods of manufacture, and methods of treatment for therapeutic applications.

Lipid-coated albumin nanoparticle compositions and methods of making and method of using the same

Lipid nanoparticle formulations, methods of making, and methods of using same are disclosed.

Prostacyclin compounds, compositions and methods of use thereof

Prostacyclin compounds and compositions comprising the same are provided herein. Specifically, prostacyclin compounds comprising treprostinil covalently linked to a linear C5-C8 alkyl, branched C5-CI8 alkyl, linear C2-C18 alkenyl, branched C3-C18 alkenyl, aryl, aryl-Ci-Cis alkyl or an amino acid or a peptide (e.g., dipeptide, tripeptide, tetrapeptide) are described. The linkage, in one embodiment, is via a carbamate, amide or ester bond. Prostacyclin compounds provided herein can also include at least one hydrogen atom substituted with at least one deuterium atom. Methods for treating pulmonary hypertension (e.g., pulmonary arterial hypertension) and portopulmonary hypertension are also provided.

Novel compositions of lipids and stabilizing materials

Lock and key micelles

Therapy for human cancers using cisplatin and other drugs or genes encapsulated into liposomes

ADHESION PROTEIN MICELLES

A micelle of an adhesion protein which naturally includes a phosphatidylinositol lipid anchor, the micelle being capable of binding multivalently to a plurality of target molecules on a cell surface. The micelle can be used to ameliorate diseases in which binding of T-cells to other cells is a continuing factor, e.g. in autoimmune diseases like rheumatoid arthritis, allograft rejection and graft-versus-host diseases.

USE OF THE TAS1R3 PROTEIN AS A MARKER FOR THERAPEUTIC, DIAGNOSTIC, AND/OR PROGNOSTIC PURPOSES FOR TUMORS THAT EXPRESS SAID PROTEIN

In the present invention, the use of the TAS1R3 receptor as a biomarker for application in cancer diagnosis, monitoring, and therapy is described for the first time. In this sense, the authors of the present invention have demonstrated that TAS1R3 is a biomarker of interest in oncology, useful for the diagnosis of the disease, and capable of providing relevant information thereupon, to monitor the evolution, select the treatment, and selectively direct therapeutic molecules. It has been determined that it is possible to identify therapies against this receptor, and that it is also possible to direct conjugates and controlled release systems of drugs, such as nanoparticles, observing a very effective intracellular accumulation thereof in primary, disseminated and metastatic tumor cells. On the other hand, the presence of TAS1R3 in circulating tumor cells (CTCs) has also been demonstrated. These are tumor cells released into the bloodstream by the primary tumor and are considered key factors ...

VAP POLYPEPTIDE AND USE THEREOF IN PREPARATION OF DRUG FOR TARGETED DIAGNOSIS AND TREATMENT OF TUMOUR

Provided in the present invention are highly stable D-configuration polypeptides DVAP and SVAP having a high binding activity to the GRP78 protein, and also provided are an L-configuration polypeptide LVAP and a DVAP-or SVAP-modified model drug and a macromolecule carrier material, and the use thereof in the construction of a tumour image and a drug-delivery system for targeted treatment.

SMALL POLYMERIC CARRIERS FOR DELIVERY OF AGENTS

A polymer includes a hydrophobic polymer backbone, a first plurality of pendant groups attached to the hydrophobic polymer backbone and including at least one group including a plurality of hydroxyl groups, and a second plurality of pendant groups attached to the hydrophobic polymer backbone and comprising at least one hydrophilic polymer.

DEVICES AND PROCESSES FOR CHERENKOV-ACTIVATED NUCLEAR-TARGETED PHOTODYNAMIC THERAPY

Devices, materials, compounds, systems, and processes for Cherenkov-Activated Nuclear-Targeted Photodynamic Therapy that involves generating Cherenkov light within the tissue of a target volume and using this light to activate photosensitizing material that is located in the nucleus of cells of the target volume.

CARRIER FOR USE IN DELIVERING DRUG, CONJUGATE, COMPOSITION COMPRISING SAME, AND METHOD FOR ADMINISTERING SAME

The present invention provides a vesicle for delivering a drug to the brain, a conjugate, a composition containing same, and a method for administering same. A composition for administration to a subject according to a dosing regimen, the composition containing a carrier for drug delivery, wherein the dosing regimen includes the administration of the composition to a subject who has been made to fast or in whom hypoglycemia has been induced and the induction of a rise in blood sugar levels in the subject, and the outer surface of the carrier in the composition is modified by a GLUT1 ligand.

DRUG DELIVERY VEHICLE COMPRISING CONJUGATES BETWEEN TARGETING POLYAMINO ACIDS AND FATTY ACIDS

The invention provide herein provides for a targeted drug delivery vehicle compositions, methods of manufacture, and methods of treatment for therapeutic applications.

NANOPARTICLES FOR IMMUNOTHERAPY

Nanoparticles that activate complement in the absence of biological molecules are described. The nanoparticles are shown to specifically target antigen presenting cells in specifically in lymph nodes, without the use of a biological molecule for targeting. These particles are useful vehicles for delivering immunotherapeutics. Surface chemistries and chemical formulations for the nanoparticles are described.

LIQUID COMPOSITION OF CISPLATIN COORDINATION COMPOUND

A liquid composition containing a polymer micelle and having a pH values of 3.0 to 7.0 is provided. The micelle is constituted of a coordination compound having a block copolymer of polyethylene glycol and polyglutamic acid and cisplatin that is coordinate-bonded to the block copolymer.

LIPID NANOPARTICLE COMPOSITIONS FOR ANTISENSE OLIGONUCLEOTIDES DELIVERY

Described is a lipid nanoparticle composition that includes a macromolecule conjugated to a polymer and a targeting agent. The composition can include a therapeutic agent. The therapeutic agent can be an antisense oligonucleotide (ASO). Exemplary ASOs are targeted to a portion of a nucleic acid encoding Akt-1, and which modulates the expression of Akt-1; or targeted to a portion of a nucleic acid encoding HIF-1, and which modulates the expression of HIF-1. Also described is a lipid nanoparticle composition that includes a macromolecule conjugated to a polymer and a therapeutic agent that is an ASO such as an ASO targeted to a portion of a nucleic acid encoding Akt-1, and which modulates the expression of Akt-1 or an ASO targeted to a portion of a nucleic acid encoding HIF-1, and which modulates the expression of HIF-1. Pharmaceutical formulations, methods of making the lipid nanoparticles, and methods of using the lipid nanoparticles, for example for treating cancers, are also disclosed ...

NANOPARTICLE COMPOSITIONS FOR GENERATION OF REGULATORY T CELLS AND TREATMENT OF AUTOIMMUNE DISEASES AND OTHER CHRONIC INFLAMMATORY CONDITIONS

The present invention relates to nanoparticles for the targeted delivery of antigen to liver cells, in particular, liver sinusoidal endothelial cells (LSEC) and/or Kupffer cells, and for the in vivo generation of regulatory T cells, notably CD4+CD25+FOXP3+ regulatory T cells (Treg). The invention provides pharmaceutical compositions and methods for the prevention and treatment of autoimmune diseases, allergies or other chronic inflammatory conditions, and for generation of regulatory T cells. The nanoparticles used in the invention comprise a) a micelle comprising an amphiphilic polymer rendering the nanoparticle water-soluble, and b) a peptide comprising at least one T cell epitope associated with the outside of the micelle. The micelle may or may not comprise a solid hydrophobic core.

UNIMOLECULAR MICELLES AND METHOD OF MAKING THE SAME

In accordance with the present invention there is provided a method of makin g a cascade polymer including the steps of alkylating the branches of a multi-branch core alkyne building block includi ng multiple ether side chains and simultaneously reducing the alkyne triple bonds and deprotecting to form a multi-hydroxyl terminated, multi-branched all alkyl polymer. The inventive method results in the formation of a unimolecular micelle consisti ng essentially of alkyl carbon.

METHODS OF TREATING COLON CANCER USING NANOPARTICLE MTOR INHIBITOR COMBINATION THERAPY

PREPARATIONS WITH CONTROLLED RELEASE FOR DELIVERY OF INHIBITORS OF HIF-1

COMPOSITION FLUOROCARBON NANOEMULSIONS, METHODS OF THEIR PRODUCTION AND USE

VACCINE ON THE BASIS OF PEPTIDES, METHODS OF THEIR MANUFACTURING AND APPLICATION FOR INDUCTION OF IMMUNE RESPONSE

LANGERIN

composições oftálmicas aquosas, método de induzir ou aumentar a formação de lágrima, método de formação de aglomerados de ciclosporina a e uso de ciclosporina a

AMPHIPHILIC POLYMER SYSTEMS

The preparation of poly-2-oxazoline amphiphilic polymers and copolymers is described. Self-assembled particles comprising these amphiphilic polymers and which are useful for the targeted delivery of therapeutic and diagnostic agents are also described.

Polymeric micellar complexes and drug delivery vehicles thereof

Disclosed are complexes of an amphiphilic copolymer, wherein the amphiphilic copolymer has benzoyl sulfonic acid groups on the hydrophobic segment of the copolymer.

POLYMER, METHOD FOR PRODUCING POLYMER, AND DRUG CONJUGATE

Provided is a polymer including a repeating unit (I) represented by Formula (I) and a repeating unit (II) represented by Formula (II) (in the formulae, m represents 1 or 2, L represents a divalent aromatic hydrocarbon group or a divalent aliphatic hydrocarbon group, R 1 represents a hydrogen atom, an aliphatic hydrocarbon group, or an aromatic hydrocarbon group, X represents OR x , SR x , or NR x1 R x2 , R x represents a hydrogen atom, an aliphatic hydrocarbon group, or an aromatic hydrocarbon group, R x1 and R x2 each independently represent a hydrogen atom, an aliphatic hydrocarbon group, or an aromatic hydrocarbon group).

Dual function polymer micelles

The invention relates to micelles that are elaborated with functionality useful for imaging and/or selectively targeting tissue, e.g., in the delivery of hydrophobic agents.

Amphiphilic [5:1]- and [3:3]- hexakisadducts of fullerenes

Herein are disclosed substituted fullerenes, comprising a fullerene core (Cn), wherein n is an even integer greater than or equal to 60; 3 or 5 dihydrocarbylmalonate (>C(COOR¹)(COOR²)) groups bonded to the fullerene core; and 1 or 3 polar extended malonate groups (>C(COOR³)(COOR⁴)) bonded to the fullerene core. The substituted fullerenes can form micelles, and can be used to ameliorate oxidative stress diseases.

MICROPARTICLES AND NANOPARTICLES HAVING SULFATE GROUPS ON THE SURFACE

This invention provides polymer particles which contain negative charges on the surface of the particle. Preferably, the particles comprise PLGA and sulfate polymer. The invention also provides polymer particle produced by the methods of the invention. 1. Particles having negative surface charges , comprising polylactide-co-glycolide (PLGA) and a sulfate polymer , such as a sulfate polysaccharide , e.g. , heparan sulfate , carrageenan , fucoidan , and ulvan.2. The particles of claim 1 , wherein the particles are microparticles or nanoparticles.3. The particles of claim 1 , wherein the particles have a zeta potential having an absolute value of at least about 25 mV claim 1 , such as at least about 40 mV.4. The particles of claim 1 , wherein the PLGA and sulfate polymer form an interpenetrating network.5. The particles of claim 1 , wherein the sulfate polymer is a sulfate polysaccharide having a molecular weight between about 200 Da and 15 kDa.6. The particles of claim 1 , further comprising an active agent.7. A method for the preparation of microparticles or nanoparticles comprising: (1) dissolving PLGA (and optionally an active agent claim 1 , such as a pharmaceutical ingredient (API) claim 1 , or a poorly water soluble compound) in a first solvent to form a PLGA solution; (2) emulsifying the polymer solution in a solution of a second solvent to form an emulsion claim 1 , wherein the first solvent is not miscible or partially miscible with the second solvent claim 1 , and wherein the solution of the second solvent comprises a sulfate polymer claim 1 , said solution of the second solvent optionally further comprising a surfactant and/or an API soluble in the second solvent; and claim 1 , (3) removing the first solvent to form said microparticles or nanoparticles having negative surface charges.8. The method of comprising: (1) dissolving PLGA (and optionally an active agent claim 7 , an API claim 7 , or a poorly water soluble compound) in a first solvent to form a ...

COMPOSITION AND DELIVERY VEHICLE FOR ACTIVE AGENTS AND METHODS THEREFOR

DIAGNOSTIC METHODS USING PGC-1? EXPRESSION

НАЦЕЛИВАЮЩИЕ АМИНОКИСЛОТНЫЕ ЛИПИДЫ

Изобретение относится к системе носителя, включающей соединение формулы I, и включает этер-липиды, конъюгированные с одним или более биоактивными лигандами, которые размещаются на поверхности системы носителя, для применения в нацеленной доставке и/или системах антигенного дисплея. Необязательно, один или более дополнительных биоактивных агентов могут быть инкапсулированы или встроены в, или присоединены к, или адсорбированы на системе носителя. Также предложены соединения формулы I, где Y представляет собой О, N, S или ковалентную связь, S, S, Sпредставляют собой независимо друг от друга ковалентную связь или группу спейсера, Х, Х, Хпредставляют независимо друг от друга Н или нацеливающий лиганд, или антигенный лиганд, или терапевтический лиганд, или диагностический лиганд, или их комбинацию, L представляет собой группу формулы (а), где пунктирная линия представляет собой связь с N, Rпредставляет собой Н, Rпредставляет собой Н, Rпредставляет собой Н, Rпредставляет собой Н или группу формулы ...

НОВЫЕ ГИДРОТРОПЫ НА ОСНОВЕ ПОЛИМЕРА ДЛЯ ДОСТАВКИ ГИДРОФОБНОГО ЛЕКАРСТВЕННОГО СРЕДСТВА

Изобретение относится к конъюгату полимера, к полимерной мицелле, образованной конъюгатом полимера, к терапевтической композиции, предназначенной для лечения рака, а также к способу лечения заболевания или состояния, которым является рак. Конъюгат полимера содержит основную цепь, представляющую собой анионный полимер, и гидрофобные составляющие, ковалентно присоединенные к основной цепи полимера. Конъюгат полимера имеет следующую формулу (I):,где М независимо выбирается из группы, состоящей из гидрофобной составляющей и катиона; гидрофобная составляющая независимо выбирается из:илиГидрофобная составляющая составляет 20-50 мол. % от общего количества М; катион независимо выбирается из водорода, аммиака или щелочного металла; X представляет собой О. Терапевтическая композиция для лечения рака содержит носитель, состоящий из вышеуказанного конъюгата полимера, и гидрофобное соединение, функционально связанное с носителем. Гидрофобным лекарственным средством является противораковое лекарственное ...

НАЦЕЛИВАЮЩИЕ АМИНОКИСЛОТНЫЕ ЛИПИДЫ

... 1. Система носителя, которая включает соединение формулы Iгде Y представляет собой O, N, S или ковалентную связь,S, S, Sпредставляют собой независимо друг от друга ковалентную связь или группу спейсера,X, Xпредставляют независимо друг от друга H или группу лиганда,L представляет собой группу формулы (а)где пунктирная линия представляет собой связь с N,Rпредставляет собой Н или группу формулы -(CH)-OR,Rпредставляет собой Н или группу формулы -(CH)-OR,Rпредставляет собой Н или группу формулы -CH-OR,Rпредставляет собой Н или группу формулы -ORили -CH-OR,Rпредставляет собой Н или группу формулы -(CH)-ORили -(CH)-OR,R, R, R, R, R, Rпредставляют независимо друг от друга насыщенную или ненасыщенную, разветвленную или неразветвленную углеводородную цепь,m равен 1, 2 или 3,при условии, что, по крайней мере, один из R, R΄, R, R΄, Rне является H и, по крайней мере, один из X, X, Xпредставляет собой группу лиганда.2. Система носителя в соответствии с п. 1, где Rпредставляет собой H, a L представляет ...

КОМПОЗИЦИЯ РАЗРУШАЮЩЕЙСЯ ПОЛИМЕРНОЙ МИЦЕЛЛЫ

... 1. Композиция полимерной мицеллы, содержащая блок-сополимеры, каждый из которых имеет гидрофобный сегмент полимерной цепи и гидрофильный сегмент полимерной цепи, при этом множество блок-сополимеров компонуются радиально в состоянии, в котором гидрофобный сегмент полимерной цепи направлен внутрь, а гидрофильный сегмент полимерной цепи направлен наружу,где композиция полимерной мицеллы в качестве блок-сополимеров содержит блок-сополимер, обладающий сродством к ЛПВП, и блок-сополимер, обладающий сродством к липопротеину за исключением ЛПВП;блок-сополимер, обладающий сродством к ЛПВП, содержит гидрофобный сегмент полимерной цепи, образованный из полиаминокислоты, включающей повторяющиеся звенья, произведенные из гидрофобного производного аминокислоты, при этом гидрофобное производное аминокислоты включает производное, полученное в результате введения в боковую цепь аминокислоты ароматической группы и/или стерольного остатка;блок-сополимер, обладающий сродством к липопротеину за исключением ...

Compositions and methods for organ specific delivery of nucleic acids

The present disclosure provides compositions which shown preferential targeting or delivery of a nucleic acid composition to a particular organ. In some embodiments, the composition comprises a steroid or sterol, an ionizable cationic lipid, a phospholipid, a PEG lipid, and a permanently cationic lipid which may be used to deliver a nucleic acid.

Hyaluronic acid derivative with urethane linkage

A biodegradable hyaluronic acid derivative comprises at least one modified hyaluronic acid repeating unit with a urethane linkage represented by the formula (HA)-[O(C = O)NH-M]p, wherein HA is a unit including N-acetyl-D-glucosamine and D-glucuronic acid, M is a modifying moiety containing a C2-16 hydrocarbyl group or a prepolymer, and p is an integer of 1 to 4. M may be a C4-12 alkyl group or a biodegradable polyester-containing prepolymer, such as polycaprolactone (PCL) or poly L-lactide (PLLA). The hyaluronic derivative may be a comb-like or brush-like shaped graft copolymer. A biodegradable polymeric micelle composition is also disclosed, whereby the hyaluronic acid derivative forms micelles in a hydrophilic medium, such as water. A pharmaceutical or bioactive composition is also claimed in which a pharmaceutically active or bioactive molecule is entrapped within micelles formed by the hyaluronic acid derivative.

Micelles

A HYDROPHOBES RECEPTOR MOLECULE FOR ANTIGENS MATERIALS OF ABSTENTIONS OF IMMUNE-STIMULATING COMPLEX (ISCOM) OR MATRIX OF BOUND ONES OF IMMUNE-STIMULATING COMPLEX (ISCOM MATRIX)

PURPOSEFUL ADMINISTRATION OF KUENSTLICHEN GENES

POLYMERE MIZELLE WITH THEREIN INCLUDING CISPLATIN AND YOUR USE

POLYMERMICELLEN FOR THE MEDICINE MATERIAL SUPPLY

POLYETHER MORE BLOCKCOPOLYMER MICELLARE COMPOSITIONS FOR THE PURPOSEFUL ADMINISTRATION OF BIOLOGICAL MATERIALS

POLYETHYLENE OXIDES WITH GROUP OF SACCHARIDES AT AN END AND ANOTHER FUNCTIONAL GROUP AT THE OTHER END AS WELL AS PROCEDURE FOR THEIR PRODUCTION

Steroid analogs and characterization and treatment methods

BLOOD CLOT-TARGETED NANOPARTICLES

Novel targeted delivery system for bioactive agents

Iscom or iscom-matrix comprising hydrophobic receptor molecules for antigenic substances

Self-assembled diblock copolymers composed of pegmema and drug bearing polymeric segments

This invention relates to polymer drug conjugates according to formula I, and their use for treatment of diseases such as cancer.

Biologically useful polyphosphates

Nanoparticles for immunotherapy

Nanoparticles that activate complement in the absence of biological molecules are described. The nanoparticles are shown to specifically target antigen presenting cells in specifically in lymph nodes, without the use of a biological molecule for targeting. These particles are useful vehicles for delivering immunotherapeutics. Surface chemistries and chemical formulations for the nanoparticles are described.

Liquid composition comprising cisplatin-coordinating compound

Self-assembling micelle-like nanoparticles for systemic gene delivery

Compositions of fluorocarbon nanoemulsion, and methods of preparation and use thereof

The invention provides novel compositions of fluorocarbon nanoemulsions comprising one or more of fluorosurfactants and phospholipids, and methods of preparation and use thereof for enhanced oxygen delivery.

Amphiphilic block copolymers, micelles, and methods for treating or preventing heart failure

Micelle-forming amphiphilic block copolymers for use in targeting cardiac cells (e.g. fibrotic cells) of a subject suffering from heart failure, micelles containing the micelle-forming amphiphilic block copolymers together with a cardioactive agent, and related compositions and methods for treating or preventing heart failure, e.g. heart failure with preserved ejection fraction (HFpEF) also known as diastolic heart failure.

Use of the TAS1R3 protein as a marker for therapeutic, diagnostic, and/or prognostic purposes for tumors that express said protein

In the present invention, the use of the TAS1R3 receptor as a biomarker for application in cancer diagnosis, monitoring, and therapy is described for the first time. In this sense, the authors of the present invention have demonstrated that TAS1R3 is a biomarker of interest in oncology, useful for the diagnosis of the disease, and capable of providing relevant information thereupon, to monitor the evolution, select the treatment, and selectively direct therapeutic molecules. It has been determined that it is possible to identify therapies against this receptor, and that it is also possible to direct conjugates and controlled release systems of drugs, such as nanoparticles, observing a very effective intracellular accumulation thereof in primary, disseminated and metastatic tumor cells. On the other hand, the presence of TAS1R3 in circulating tumor cells (CTCs) has also been demonstrated. These are tumor cells released into the bloodstream by the primary tumor and are considered key factors ...

COMPOSITES AND COMPOSITIONS FOR THERAPEUTIC USE AND METHODS OF MAKING AND USING THE SAME

Disclosed herein are embodiments of composites and compositions that can be used for therapeutic applications in vivo and/or in vitro. The disclosed composites can comprise cores having magnetic nanoparticles, quantum dots, or combinations thereof and zwitterionic polymeric coatings that facilitate solubility and bioconjugation. The compositions disclosed herein can comprise the composites and one or more biomolecules, drugs, or combinations thereof. Also disclosed herein are methods of making the composites, composite components, and methods of making quantum dots for use in the composites.

NANOSYSTEMS AS SELECTIVE VEHICLES

In the present invention, the development of various oil-in-water (O / W) nanoemulsions containing an oil phase or oil core, preferably selected from vitamin E or oleic acid, stabilized by a sphingolipid of the sphingomyelin type, and optionally other lipids such as phospholipids, cholesterol, octadecylamine, DOTAP (N- [1- (2,3-Dioleoyloxy) propyl] -N, N, N-trimethylammonium methyl-sulfate), and PEGylated derivatives (derivatives with polyethylene glycol), for use as a nanotech vehicle, in particular for the management of cancer and metastatic disease, is herein described. Said nanoemulsions can be functionalized with ligands capable of interacting or binding to receptors expressed on the cell membrane of tumor cells, and in particular capable of interacting or binding to receptors expressed on the membrane of primary and/or disseminated or metastatic tumor cells. Also, antitumor drugs or therapeutic biomolecules can be encapsulated in said nanoemulsions and, finally, contrast agents can ...

NOVEL POLY(ETHYLENE OXIDE)-BLOCK-POLY(ESTER) BLOCK COPOLYMERS

The present invention relates to micelle-forming poly(ethylene oxide)-block-poly(ester) block copolymers having reactive groups on the polyester block therein. The biodegradability of these copolymers and their biocompatibilities with a large number of bioactive agents make them suitable as carriers for various bioactive agents. The bioactive agents, such as DNA, RNA, oligonucleotide, protein, peptide, drug and the like, can be coupled to the reactive groups on the polyester block of the copolymer.

NANOPARTICLES FOR IMMUNOTHERAPY

Nanoparticles that activate complement in the absence of biological molecules are described. The nanoparticles are shown to specifically target antigen presenting cells in specifically in lymph nodes, without the use of a biological molecule for targeting. These particles are useful vehicles for delivering immunotherapeutics. Surface chemistries and chemical formulations for the nanoparticles are described.

COMPOSITIONS AND METHODS FOR SILENCING APOLIPOPROTEIN C-III EXPRESSION

The present invention provides compositions comprising therapeutic nucleic acids such as interfering RNA that target apolipoprotein C-III (APOC3) gene expression, lipid particles comprising one or more (e.g., a cocktail) of the therapeutic nucleic acids, methods of making the lipid particles, and methods of delivering and/or administering the lipid particles (e.g., for the treatment of lipid diseases or disorders such as atherosclerosis or a dyslipidemia such as hypertriglyceridemia or hypercholesterolemia).

TUNABLE, BIODEGRADABLE LINKER MOLECULES FOR TRANSIENT CONJUGATION OF COMPONENTS IN DRUG DELIVERY SYSTEMS, AND DRUG DELIVERY SYSTEMS PREPARED THEREWITH

The present invention relates to a particular class of biodegradable linkers, ensuring transiently stable conjugation of building blocks and/or bioactive compounds into drug delivery systems (DDS), such as DDS based on polymeric micelles or hydrogels. In addition, the present invention relates to compounds, comprising said linkers, such compounds preferably being prodrugs. Further, the invention is directed to the use of said linkers, and especially said biodegradable linkers, in a drug delivery system. Moreover, the invention relates to controlled release system comprising a polymer matrix, capable of releasing an active ingredient, wherein the active ingredient is covalently linked to the polymer molecules of the polymer matrix through said linkers, as well as to a method of synthesising these linkers and preparing such controlled release systems.

METHODS AND COMPOSITIONS RELATED TO CLOT-BINDING LIPID COMPOUNDS

Disclosed are compositions and methods related to clot-binding head groups. The disclosed targeting is useful for treatment of cancer and other diseases and disorders.

LIPID NANOPARTICLE COMPOSITIONS AND METHODS OF MAKING AND METHODS OF USING THE SAME

Lipid nanoparticle formulations, methods of making, and methods of using same are disclosed.

NEUROTHERAPEUTIC NANOPARTICLE COMPOSITIONS AND DEVICES

There are provided compositions and methods for treatment of neurodegeneative diseases and CNS injury. The compositions a pharmaceutically acceptable carrier solution; and a plurality of biodegradable nanoparticles, wherein the nanoparticles comprise a targeting moiety that is able to bind selectively to the surface of a neural stem cell and wherein the nanoparticles further comprise factors such as leukaemia inhibitory factor (LIF); XAV939 and/or one or more of : brain- derived neurotrophic factor (BDNF) or an agonist thereof; epidermal growth factor (EGF) or an agonist thereof; glial cell-derived neurotrophic factor (GDNF) or an agonist thereof; retinoic acid and derivatives thereof; ciliary neurotrophic factor (CTNF) or an agonist thereof; and Wnt5A. The biodegradable nanoparticles may deliver via controlled time release.

[SAMOSOBIRAYUSHCHIESYA] AMPHIPHILIC POLYMERS AS THE ANTITUMORIGENIC MEANS

Nanometer preparation of anticancer natural product (gambogic acid) and preparation method thereof

ENCAPSULATION Of LIPOPHILIC OR AMPHIPHILIC THERAPEUTIC AGENTS IN NANOEMULSIONS

La présente invention vise une formulation d'agent thérapeutique sous forme de nanoémulsion, comprenant une phase aqueuse continue et au moins une phase huileuse dispersée, dans laquelle la phase huileuse comprend outre l'agent thérapeutique au moins un lipide amphiphile et au moins un lipide solubilisant et dans laquelle la phase aqueuse comprend au moins un co-tensioactif polyalkoxylé. Elle vise également un procédé de préparation et l'utilisation de cette formulation.

MICELLE FOR INCLUDING AIR BUBBLE FOR CARRYING DRUG AND METHOD FOR MAKING THE MICELLE

A NANOPARTICLE SUITABLE FOR DELIVERY OF A BIOMOLECULE INTO OR OUT OF A MEMBRANE ENCLOSED CELL OR CELL ORGANELLE

CONTROLLED RELEASE SYSTEM

TARGETING AMINOACID LIPIDS

GUGGULPHOSPHOLIPID METHODS AND COMPOSITIONS

The present invention relates to the methods for preparing synthetic guggulphospholipids, their fatty acid analogues and other bioactive molecules. The present invention relates to E-guggulsterone and Z-guggulsterone or mixture of E- and Z-guggulsterones, and E-guggulsterol and Z-guggulsterol or mixture of E- and Z-guggulsterols synthetically modified to guggulphospholipids and analogues and salts thereof, fatty acid analogues of guggulsterols, guggulsulfate and salts thereof, guggulphosphate and salts thereof; and guggulsterols conjugated with drugs for use as prodrugs. Also the present invention provides a novel method for the preparation of E-guggulsterol and Z-guggulsterol or mixture of E- and Z-guggulsterols from a mixture of E- and Z-guggulsterones. The present invention further relates to guggulphospholipids and other bioactive molecules incorporated into complexes such as liposomes, complexes, emulsions, vesicles, micelles, and mixed micelles, which can include other active agents ...

NANOCARRIERS FOR DRUG DELIVERY

The present invention provides a nanocarrier having an interior and an exterior, the nanocarrier comprising at least one conjugate, wherein each conjugate includes a polyethylene glycol (PEG) polymer. Each conjugate also includes at least two amphiphilic compounds having both a hydrophilic face and a hydrophobic face. In addition, each conjugate includes an oligomer, wherein at least 2 of the amphiphilic compounds are covalently attached to the oligomer which is covalently attached to the PEG. The nanocarrier is such that each conjugate self-assembles in an aqueous solvent to form the nanocarrier such that a hydrophobic pocket is formed in the interior of the nanocarrier by the orientation of the hydrophobic face of each amphiphilic compound towards each other, and wherein the PEG of each conjugate self-assembles on the exterior of the nanocarrier.

Block Copolymer For Intraperitoneal Administration Containing Anti-Cancer Agent, Micelle Preparation Thereof, And Cancer Therapeutic Agent Comprising The Micelle Preparation As Active Ingredient

To provide a therapeutic method using a water soluble, high molecular weight block polymer to enable that an intraperitoneally administered anti-cancer agent may maintain for a long-term retention in the abdominal cavity to enoughly exert the effect of the anti-cancer agent and reduce adverse side-effects thereof. A therapeutic agent as a micelle preparation, comprising a copolymer having a hydrophilic polymeric moiety and a polycarboxylic acid derivative moiety; and an anti-cancer agent bonding to or encapsulated in the copolymer, wherein the micelle preparation may exhibit sustained drug release capability, and enables an extension of a retention time period of the anti-cancer agent in an abdominal cavity, is provided. A superior life-prolonging effect was found in an intraperitoneal administration mouse model compared with a case in which only an encapsulated drug is administered, and thus the present invention was completed accordingly.

Prodrug compositions, prodrug nanoparticles, and methods of use thereof

Nanoparticles comprising a prodrug and prodrugs linked to phospholipids, wherein the linkages facilitate release of the prodrugs from the nanoparticles to sites within a target cell or cell membrane by fusion of the particle and the cell membrane are disclosed. Also disclosed are methods for producing and using the nanoparticles and their constituents.

Anti-CD74 Immunoconjugates and Methods of Use

Disclosed are compositions that include anti-CD74 immunoconjugates and optionally a therapeutic and/or diagnostic agent. In preferred embodiments, the immunoconjugates comprise one or more anti-CD74 antibodies or antigen-binding fragments thereof, conjugated to a liposome or micelle. Also disclosed are methods for preparing the immunoconjugates and using the immunoconjugates in diagnostic and therapeutic procedures. In certain preferred embodiments, the therapeutic methods comprise administering to a subject with a CD74-expressing disease an anti-CD74 immunoconjugate and thereby inducing apoptosis of CD74-expressing cells. In more preferred embodiments, the CD74 immunoconjugate is capable of inducing cell death in the absence of any other therapeutic agent, although such agents may be optionally administered prior to, together with or subsequent to administration of the anti-CD74 immunoconjugate. The compositions may be part of a kit for administering the anti-CD74 immunoconjugates or compositions.

Tunable, biodegradable linker molecules for transient conjugation of components in drug delivery systems, and drug delivery systems prepared therewith

The present invention relates to a particular class of biodegradable linkers, ensuring transiently stable conjugation of building blocks and/or bioactive compounds into drug delivery systems (DDS), such as DDS based on polymeric micelles or hydrogels. In addition, the present invention relates to compounds, comprising said linkers, such compounds preferably being prodrugs. Further, the invention is directed to the use of said linkers, and especially said biodegradable linkers, in a drug delivery system. Moreover, the invention relates to controlled release system comprising a polymer matrix, capable of releasing an active ingredient, wherein the active ingredient is covalently linked to the polymer molecules of the polymer matrix through said linkers, as well as to a method of synthesising these linkers and preparing such controlled release systems.

Polymersomes, liposomes, and other species associated with fluidic droplets

The present invention relates generally to vesicles such as liposomes, colloidosomes, and polymersomes, as well as techniques for making and using such vesicles. In some cases, the vesicles may be at least partially biocompatible and/or biodegradable. The vesicles may be formed, according to one aspect, by forming a multiple emulsion comprising a first droplet surrounded by a second droplet, which in turn is surrounded by a third fluid, where the second droplet comprises lipids and/or polymers, and removing fluid from the second droplet, e.g., through evaporation or diffusion, until a vesicle is formed. In certain aspects, the size of the vesicle may be controlled, e.g., through osmolarity, and in certain embodiments, the vesicle may be ruptured through a change in osmolarity. In some cases, the vesicle may contain other species, such as fluorescent molecules, microparticles, pharmaceutical agents, etc., which may be released upon rupture. Yet other aspects of the invention are generally directed to methods of making such vesicles, kits involving such vesicles, or the like.

Block Copolymer For Intraperitoneal Administration Containing Anti-Cancer Agent, Micelle Preparation Thereof, And Cancer Therapeutic Agent Comprising The Micelle Preparation As Active Ingredient

To provide a therapeutic method using a water soluble, high molecular weight block polymer to enable that an intraperitoneally administered anti-cancer agent may maintain for a long-term retention in the abdominal cavity to enoughly exert the effect of the anti-cancer agent and reduce adverse side-effects thereof. A therapeutic agent as a micelle preparation, comprising a copolymer having a hydrophilic polymeric moiety and a polycarboxylic acid derivative moiety; and an anti-cancer agent bonding to or encapsulated in the copolymer, wherein the micelle preparation may exhibit sustained drug release capability, and enables an extension of a retention time period of the anti-cancer agent in an abdominal cavity, is provided. A superior life-prolonging effect was found in an intraperitoneal administration mouse model compared with a case in which only an encapsulated drug is administered, and thus the present invention was completed accordingly.

MELANOCORTIN 1 RECEPTOR LIGANDS AND METHODS OF USE

The subject invention pertains to a modified MC1R peptide ligand comprising a peptide that is a melanocortin 1 receptor (MC1R) ligand and a functionality or linker, such as a click functionality, for conjugation to a surface or agent. The modified MC1R peptide ligand can be coupled, e.g., via a click reaction with a complementary click functionality attached, to a moiety to form an MC1R-targeted agent. Drugs, contrast agents, polymers, particles, micelles, surfaces of larger structures, or other moieties can be targeted to the MC1R. The subject invention also pertains to a MC1R peptide ligand-micelle complex comprising a peptide that is a melanocortin 1 receptor ligand connected via a click reaction product to a micelle. The micelle is stable in vivo and can target melanoma tumor cells by association of the peptide ligand with the MC1R or the tumor and selectively provide a detectable and/or therapeutic agent (such as an imageable contrast agent and/or anti-cancer agent) selectively to the tumor cell. 1. A modified melanocortin 1 receptor (MC1R) peptide ligand , comprising an MC1R peptide ligand coupled to a functionality.2. The modified MC1R peptide ligand of claim 1 , wherein said functionality is an alkyne claim 1 , azide claim 1 , amine claim 1 , aldehyde claim 1 , thiol claim 1 , alkene claim 1 , ester claim 1 , or maleimide.3. The modified MC1R peptide ligand of claim 1 , wherein said functionality is coupled to the C-terminus of said MC1R ligand.4. The modified MC1R peptide ligand of claim 1 , wherein said functionality is coupled to the N-terminus of said MC1R ligand.6. The modified MC1R peptide ligand of claim 1 , wherein said MC1R peptide ligand comprises the amino acid motif His-Phe-Arg-Trp (HFRW) (SEQ ID NO:1).7. The modified MC1R peptide ligand of claim 1 , wherein said MC1R peptide ligand comprises the amino acid motif His-DPhe-Arg-Trp (HfRW) (SEQ ID NO:2).8. A method selected from among:(a) a method of preparing a MC1R peptide ligand comprising an ...

TOLL-LIKE RECEPTOR 7 OR 8 AGONIST-CHOLESTEROL COMPLEX AND METHOD OF PREPARING SAME

The present disclosure relates to a toll-like receptor 7/8 agonist-cholesterol complex comprising: a cholesterol; and a toll-like receptor 7/8 agonist, wherein the cholesterol is linked to an active site of the toll-like receptor 7/8 agonist. 1. A toll-like receptor 7/8 agonist-cholesterol complex comprising:a cholesterol; anda toll-like receptor 7/8 agonist,wherein the cholesterol is linked to an active site of the toll-like receptor 7/8 agonist.2. The complex of claim 1 , wherein the cholesterol is linked to the active site of the toll-like receptor 7/8 agonist by a separable linkage.3. The complex of claim 2 , wherein the separable linkage is a cleavable chemical bond selected from the group consisting of a carbamate claim 2 , a disulfide claim 2 , an ester claim 2 , a peptide claim 2 , an azide claim 2 , and a combination thereof.4. The complex of claim 1 , wherein the toll-like receptor 7/8 agonist is selected from the group consisting of an imidazoquinoline-based agonist claim 1 , a hydroxyadenine-based agonist claim 1 , a pteridone-based agonist claim 1 , an aminopyrimidine-based agonist claim 1 , a benzoazepine-based agonist claim 1 , a thia-oxoguanosine-based agonist claim 1 , a derivative thereof claim 1 , and a combination thereof.5. The complex of claim 1 , wherein the toll-like receptor 7/8 agonist is selected from the group consisting of imiquimod claim 1 , resiquimod claim 1 , dactolisib claim 1 , gardiquimod claim 1 , sumanirole claim 1 , motolimod claim 1 , vesatolimod claim 1 , loxoribine claim 1 , SM360320 claim 1 , CL264 claim 1 , 3M-003 claim 1 , IMDQ claim 1 , and Compound 54.6. The complex of claim 2 , wherein the separable linkage is a cleavable chemical bond at a linkage site in response to a tumor microenvironment claim 2 , an endosomal enzyme claim 2 , a lysosomal enzyme claim 2 , or pH in cells claim 2 , and the active site of the toll-like receptor 7/8 agonist is exposed by cleavage of the separable linkage claim 2 , thereby recovering a ...

NANOPARTICLE CONJUGATES OF HIGHLY POTENT TOXINS AND INTRAPERITONEAL ADMINISTRATION OF NANOPARTICLES FOR TREATING OR IMAGING CANCER

Disclosed are methods of treating cancer of the intraperitoneal cavity using compositions comprising nanoparticles without targeting agents. In addition, nanoparticles are described that comprise a highly toxic anticancer agent (e.g., an anticancer agent having an ICless than 1 nM) covalently bound via a linker to a triblock copolymer. Other nanoparticles that comprise Pt(IV) and an anticancer agent are also described. Also disclosed are nanoparticles comprising imaging agents non-covalently associated with a polymer, and methods of imaging cancer of the intraperitoneal cavity using compositions comprising nanoparticles without targeting agents. 2. The method of claim 1 , wherein the composition does not comprise a targeting agent.3. The method of claim 1 , wherein the particle does not comprise a targeting agent.4. The method of claim 1 , wherein the cancer is a cancer that spreads by peritoneal carcinomatosis.5. The method of claim 1 , wherein the cancer is ovarian claim 1 , gastric claim 1 , appendiceal claim 1 , liver claim 1 , pancreatic claim 1 , colorectal claim 1 , uterine claim 1 , lobular breast claim 1 , cervical claim 1 , or primary peritoneal cancer.6. (canceled)7. The method of claim 1 , wherein the biodegradable core comprises a second polymer.8. The method of claim 1 , wherein the anticancer agent has an ICof less than 1 nM.9. The method of claim 1 , wherein the polymer is a diblock copolymer comprising a first block and a second block; and the first block comprises the plurality of first monomers.10. The method of claim 9 , wherein each first monomer is selected from the group consisting of ethylene glycol and propylene glycol.11. The method of claim 9 , wherein each first monomer is ethylene glycol.12. The method of claim 1 , wherein the biodegradable core further comprisesa block copolymer comprising:(i) a first block comprising a plurality of first monomers, wherein each first monomer is selected from the group consisting of ethylene glycol, ...

POLYION COMPLEX CAPABLE OF EFFICIENTLY DELIVERING MRNA INTO LIVING BODY, AND DRUG AND METHOD FOR TREATING ARTHROPATHY IN WHICH SAID COMPLEX IS USED

The present invention provides a polyion complex which can efficiently deliver mRNA into a living body as well as a therapeutic agent and a therapeutic method of arthropathy in which the polyion complex is used. For example, there is provided a polyion complex comprising a cationic polymer and mRNA, wherein the cationic polymer is a polymer comprising a cationic unnatural amino acid as a monomer unit and the cationic unnatural amino acid is an amino acid having a group represented by —(NH—(CH))—NH, wherein p is 2, 3 or 4, as a side chain. 1: A polyion complex comprising a cationic polymer and mRNA ,{'sub': 2', '2', 'p', '2, 'wherein the cationic polymer is a polymer comprising a cationic unnatural amino acid as a monomer unit and the cationic unnatural amino acid is an amino acid having a group represented by —(NH—(CH))—NH, wherein p is 2, 3 or 4, as a side chain.'}2: The polyion complex according to claim 1 , wherein the cationic polymer is a block copolymer with polyethylene glycol.4: A pharmaceutical composition for treating arthropathy claim 1 , comprising the polyion complex according to claim 1 ,wherein the mRNA is an mRNA of a factor promoting joint formation.5: The pharmaceutical composition according to claim 4 , wherein p is 3 or 4.6: The pharmaceutical composition according to claim 5 , wherein p is 4.7: The pharmaceutical composition according to claim 4 , wherein the pharmaceutical composition is formulated for administration once every 2 days or once every 3 days.8: The pharmaceutical composition according to claim 5 , wherein the pharmaceutical composition is formulated for administration once every 7 days.9: The pharmaceutical composition according to claim 4 , wherein the arthropathy is osteoarthritis or rheumatoid arthritis.10: A delivery agent suitable for use in delivering mRNA into cells claim 3 , comprising the polyion complex according to claim 3 , wherein p is 3 or 4.11: The delivery agent according to claim 10 , wherein p is 4. This ...

Glypican-3 Peptide Reagents and Methods

The present invention is directed to glypican-3-specific peptide reagents, methods for detecting hepatocellular carcinoma cells using the peptide reagents, and methods for targeting hepatocellular carcinoma cells using the peptide reagents. 1. A reagent comprising a glypican-3-specific peptide ALLANHEELFQT (SEQ ID NO: 1) , ALLANHEELF (SEQ ID NO: 2) , GLHTSATNLYLH (SEQ ID NO: 3) , SGVYKVAYDWQH (SEQ ID NO: 4) , or VGVESCASRCNN (SEQ ID NO: 5) , or a multimer form of the peptide ,wherein the peptide specifically binds to glypican-3 andwherein at least one detectable label, at least one therapeutic moiety, or both, are attached to the peptide or a multimer form of the peptide.2. The reagent of comprising at least one detectable label attached to the peptide.3. The reagent of wherein the detectable label is detectable by microscopy claim 2 , photoacoustic claim 2 , ultrasound claim 2 , PET claim 2 , SPECT claim 2 , or magnetic resonance imaging.4. The reagent of wherein the label detectable by microscopy is fluorescein isothiocyanate (FITC).5. The reagent of wherein the label detectable by microscopy is Cy5.6. The reagent of wherein the label detectable by microscopy is Cy5.5.7. The reagent of wherein the label detectable by microscopy is IRdye800.8. The reagent of wherein the multimer form of the peptide is a dimer formed with an aminohexanoic acid linker.9. The reagent of wherein the detectable label is attached to the peptide by a peptide linker.10. The reagent of wherein a terminal amino acid of the linker is lysine.11. The reagent of wherein the linker comprises the sequence GGGSK set out in SEQ ID NO: 7.12. The reagent of 1 claim 10 , 2 claim 10 , 3 claim 10 , 4 claim 10 , 5 claim 10 , 6 claim 10 , 7 claim 10 , 8 claim 10 , 9 claim 10 , 10 or 11 comprising at least one therapeutic moiety attached to the peptide.13. The reagent of wherein the therapeutic moiety is chemotherapeutic agent.14. The reagent of wherein the therapeutic moiety is a micelle.15. The reagent of ...

SUPRAMOLECULAR GLYCOSAMINOGLYCANS

Provided herein are glycosylated peptide amphiphiles (GPAs), supramolecular glyconanostructures assembled therefrom, and methods of use thereof. In particular, provided herein are glycosaminoglycan (GAG) mimetic peptide amphiphiles (PAs) and supramolecular GAG mimetic nanostructures assembled therefrom that mimic the biological activities of GAGs, such as heparin, heparan sulfate, hyaluronic acid etc. 1. A composition comprising a supramolecular glyconanostucture , the supramolecular glyconanostucture comprising a nanofiber of glycosylated peptide amphiphiles (GPAs) self-assembled into a nanofiber; wherein the GPAs comprise a hydrophobic non-peptide tail , a structured peptide segment , a charged peptide segment , and a terminal saccharide; and wherein the nanofiber comprises a hydrophobic core , peptide surface , and saccharides displayed on the surface.2. The composition of claim 1 , further comprising filler peptide amphiphiles (PAs) claim 1 , wherein the filler PAs comprise a hydrophobic non-peptide tail claim 1 , a structured peptide segment claim 1 , and a charged peptide segment claim 1 , but lack a terminal saccharide.3. The composition of claim 2 , further comprising non-glycosylated bioactive PAs claim 2 , wherein the non-glycosylated bioactive comprise a hydrophobic non-peptide tail claim 2 , a structured peptide segment claim 2 , a charged peptide segment claim 2 , and a non-saccharide bioactive terminal moiety.4. The composition of claim 1 , wherein the saccharide is conjugated to the charged peptide by a linker.5. The composition of claim 1 , wherein the saccharide is selected from the group consisting of monosaccharide claim 1 , disaccharide claim 1 , oligosaccharide claim 1 , and glycomimetic.6. The composition of claim 5 , wherein the saccharide is selected from:(a) the monosaccharides consisting of GlcA, GlcNAc, GlcNS, IdoA, and sulfated versions thereof;(b) dissacharides of GlcA, GlcNAc, GlcNS, IdoA, and sulfated versions thereof;(c) ...

Nanoparticles for active agent delivery to brain cancers

The present invention is directed to targeted micelle active agent carriers. The carriers suitably include micelle forming components, along with pH sensitive molecules, and targeting moieties. They are useful in the treatment of various brain cancers.

MACROMOLECULAR CHEMOTHERAPEUTICS

Embodiments of the invention are directed to a macromolecular chemotherapeutic. A non-limiting example of the macromolecular chemotherapeutic includes a block copolymer. The block copolymer can include a water-soluble block, a cationic block, and a linker, wherein the linker is connected to the water-soluble bock and the charged block. 1. A macromolecular chemotherapeutic , comprising: a water-soluble block,', 'a cationic block, the cationic block comprising a polymeric subunit comprising a polycarbonate backbone having from 4 to 8 atoms; and', 'a linker, wherein the linker is connected to the water-soluble bock and the charged block., 'a block copolymer comprising2. The macromolecular chemotherapeutic of claim 1 , wherein the water-soluble block comprises polyethylene oxide.3. The macromolecular chemotherapeutic of claim 2 , wherein the polyethylene oxide has an average molecular weight of 2000 to 20 claim 2 ,000 daltons.4. The macromolecular chemotherapeutic of claim 1 , wherein the linker is a cleavable linker.5. The macromolecular chemotherapeutic of claim 3 , wherein the cleavable linker comprises an acetal or a disulfide.6. The macromolecular chemotherapeutic of claim 1 , wherein the cationic block includes polymeric subunit comprising a polycarbonate backbone having from 6 to 8 atoms.8. A method of inhibiting cancer stem cell growth comprising:providing a culture of cancer cells, comprising a plurality of cancer stem cells;incubating the cancer stem cells with a solution comprising a plurality of micelles, wherein the micelles comprise the macromolecular chemotherapeutic.9. A method of treating cancer claim 1 , comprising:administering to a mammal in need thereof an effective amount of a pharmaceutical composition, wherein the pharmaceutical composition comprises a block copolymer comprising:a water-soluble block,a cationic block, anda cleavable linker, wherein the cleavable linker is connected to the water-soluble bock and the charged block.10. The method of ...

IMMOLATIVE CELL-PENETRATING COMPLEXES FOR NUCLEIC ACID DELIVERY

There are provided herein, inter alia, complexes, compositions and methods for the delivery of therapeutic, diagnostic and imaging agents, including nucleic acid, into a cell. The complexes, compositions and methods may facilitate complexation, protection, delivery and release of oligonucleotides and polyanionic cargos into target cells, tissues, and organs both in vitro and in vivo. 1. A cell-penetrating complex comprising a nucleic acid non-covalently bound to a cationic amphipathic polymer , said cationic amphipathic polymer comprising a pH-sensitive immolation domain.2. The cell-penetrating complex of claim 1 , wherein said cationic amphipathic polymer comprises a pH-sensitive immolation domain and a lipophilic polymer domain.3. The cell-penetrating complex of claim 2 , wherein said cationic amphipathic polymer has the formula:{'br': None, 'sup': 1A', '1', '1', '2', '2', '2A, 'sub': z1', 'z2', 'z3', 'z4', 'z5, 'R-[L-[(LP)-(IM)-(LP)]-L-R]'}wherein{'sup': '1A', 'sub': 3', '3', '3', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '4', '2', '2', '2', '2', '2', '2', '2', '3', '3', '3', '3', '2', '2', '2', '2', '2', '2', '2', '2, 'Ris hydrogen, halogen, —CCl, —CBr, —CF, —CI, CHCl, —CHBr, —CHF, —CHI, —CHCl, —CHBr, —CHF, —CHI, —CN, —OH, —NH, —COOH, —CONH, —NO, —SH, —SOH, —SOH, —SONH, —NHNH, —ONH, —NHC(O)NHNH, —NHC(O)NH, —NHSOH, —NHC(O)H, —NHC(O)OH, —NHOH, —OCCl, —OCF, —OCBr, —OCI, —OCHCl, —OCHBr, —OCHI, —OCHF, —OCHCl, —OCHBr, —OCHI, —OCHF, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;'}{'sup': '2A', 'sub': 3', '3', '3', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '4', '2', '2', '2', '2', '2', '2', '2', '3', '3', '3', '3', '2', '2', '2', '2', '2', '2', '2', '2, 'Ris hydrogen, halogen, —CCl, —CBr, —CF, —CI, CHCl, —CHBr, —CHF, —CHI, —CHCl, ...

ENHANCING SUBCUTANEOUS INJECTION AND TARGET TISSUE ACCUMULATION OF NANOPARTICLES VIA CO-ADMINISTRATION WITH MACROPINOCYTOSIS INHIBITORY NANOPARTICLES (MINP)

Provided herein are multi-nanoparticle formulations. Also provided herein are methods for enhancing circulation time and/or cell-targeting efficacy of an effector nanoparticle by administering an endocytosis inhibitory nanoparticle and an effector nanoparticle. 1. A multi-nanoparticle formulation comprising: (a) a nanostructure comprising a poly(ethylene glycol)-block-poly(propylene sulfide) (PEG-b-PPS) copolymer; and', '(b) a endocytosis inhibitor loaded in the nanostructure; and, '(1) an endocytosis inhibitory nanoparticle comprising(2) an effector nanoparticle (E-NP).2. The formulation of claim 1 , wherein the endocytosis inhibitory nanoparticle is a macropinocytosis inhibitory nanoparticle (MiNP).3. The formulation of claim 1 , wherein the effector nanoparticle comprises a poly(ethylene glycol)-block-poly(propylene sulfide) (PEG-b-PPS) copolymer.4. The formulation of claim 3 , wherein the effector nanoparticle further comprises a targeting moiety incorporated into the surface of the nanoparticle claim 3 , optionally the targeting moiety comprising:(a) a cell-receptor-binding molecule;(b) a polyethylene glycol (PEG) linker; and(c) an anchor.5. The formulation of claim 4 , wherein (a) the cell-receptor-binding molecule is folate claim 4 , (b) the anchor is a palmitoleic acid lipid anchor or both (a) and (b).6. The formulation of claim 1 , wherein the effector nanoparticle further comprises a therapeutic payload.7. The formulation of claim 1 , wherein the nanostructure is a micelle or a bicontinuous nanosphere.8. A method for enhancing circulation time and/or cell-targeting efficacy of an effector nanoparticle in a subject claim 1 , the method comprising administering the formulation of .9. The method of claim 8 , wherein the administering is performed subcutaneously or intravenously.10. The method of claim 9 , wherein uptake of the effector nanoparticle by the mononuclear phagocyte system (MPS) is inhibited.11. The method of claim 8 , wherein the method does not ...

TERNARY MICELLAR COMPLEX COMPOSED OF A SIALOGLYCOSPHINGOLIPID, A THERAPEUTICALLY ACTIVE SUBSTANCE AND AN ANTIBODY

The invention relates to a pharmaceutical composition soluble in an aqueous solution, which is characterised in that it comprises sialoglycosphingolipids; polypeptides selected from the group comprising antibodies, fragments and variants of same; and at least one therapeutically active substance, forming a ternary micellar complex of sialoglycosphingolipid-therapeutically active substance-polypeptide in which the polypeptides are non-covalently associated with the micelles formed by the sialoglycosphingolipid and the therapeutically active substance. 1. A pharmaceutical compound soluble in aqueous solution comprising:at least a sialoglycosphingolipid; at least one polypeptide selected from the group consisting of antibodies, fragments and variants thereof; and at least one therapeutically active substance; wherein a ternary micellar complex if formed; and wherein said polypeptides are associated in a non-covalent manner with the micelles formed by said sialoglycosphingolipids and said therapeutically active substance.2. The pharmaceutical composition of characterized in that said sialoglycosphingolipids are selected from the group consisting of monosialogangliosides claim 1 , disialogangliosides claim 1 , trisialoganglioside claim 1 , GM1 claim 1 , LIGA-GM1 claim 1 , GM2 claim 1 , GD1a claim 1 , GD1b claim 1 , GT1 claim 1 , and mixtures thereof.3. The pharmaceutical composition of characterized in that said polypeptides are selected from the group consisting of polyclonal human antibodies claim 1 , polyclonal humanized antibodies claim 1 , polyclonal antibodies of animal origin claim 1 , monoclonal antibodies of animal origin claim 1 , chimeric antibodies claim 1 , fragments thereof claim 1 , and mixtures thereof.4. The pharmaceutical composition of characterized in that said therapeutically active substance is selected from the group consisting of antitumor drugs claim 1 , antifungal drugs claim 1 , hydrophobic drugs claim 1 , hydrophilic drugs claim 1 , taxanes ...

PORPHYRIN MODIFIED TELODENDRIMERS

The present invention provides amphiphilic telodendrimers that aggregate to form nanocarriers characterized by a hydrophobic core and a hydrophilic exterior. The nanocarrier core may include amphiphilic functionality such as cholic acid or cholic acid derivatives, and the exterior may include branched or linear poly(ethylene glycol) segments. Nanocarrier cargo such as hydrophobic drugs and other materials may be sequester in the core via non-covalent means or may be covalently bound to the telodendrimer building blocks. Telodendrimer structure may be tailored to alter loading properties, interactions with materials such as biological membranes, and other characteristics. 119.-. (canceled)22. The nanocarrier of claim 20 , wherein the nanocarrier further comprises a hydrophobic drug or an imaging agent claim 20 , such that the hydrophobic drug or imaging agent is sequestered in the hydrophobic pocket of the nanocarrier.23. The nanocarrier of claim 20 , wherein at least one of the monomer units is optionally linked to a member selected from the group consisting of an optical probe claim 20 , a radionuclide claim 20 , a paramagnetic agent claim 20 , a metal chelate and a drug.24. The nanocarrier of claim 22 , wherein the hydrophobic drug is selected from the group consisting of bortezomib claim 22 , paclitaxel claim 22 , SN38 claim 22 , camptothecin claim 22 , etoposide and doxorubicin claim 22 , docetaxel claim 22 , daunorubicin claim 22 , VP16 claim 22 , prednisone claim 22 , dexamethasone claim 22 , vincristine claim 22 , vinblastine claim 22 , temsirolimus claim 22 , carmusine claim 22 , sorafinib claim 22 , lapatinib claim 22 , and bortezomiob.25. The nanocarrier of claim 20 , wherein the nanocarrier further comprises a metal cation chelated to the porphyrin.26. The nanocarrier of claim 20 , wherein the nanocarrier further comprises a radio-metal cation selected from the group consisting of Cu claim 20 , Cu claim 20 , Lu claim 20 , Ga claim 20 , In claim 20 , and ...

Multiblock copolymers

Provided herein are multiblock copolymers, as well as micelles and therapeutic compositions thereof.

CANCER THERAPEUTICS

Disclosed herein are methods of treating pancreatic cancer and/or multiple myeloma cancer in a subject, comprising: providing a composition comprising a micelle construct attached to curcumin; and treating pancreatic cancer and/or multiple myeloma cancer in the subject by administering a therapeutically effective dosage of the composition to the subject. Further disclosed herein are pharmaceutical compositions, comprising: an inhibitor of NF-kB; a glut-1 antibody; and a pharmaceutically acceptable carrier. Also disclosed herein are methods of using the same. 1. A method of treating pancreatic cancer and/or multiple myeloma cancer in a subject , comprising:providing a composition comprising a micelle construct attached to curcumin; andtreating pancreatic cancer and/or multiple myeloma cancer in the subject by administering a therapeutically effective dosage of the composition to the subject.2. The method of claim 1 , wherein the micelle construct further comprises doxorubicin.3. The method of claim 1 , wherein the micelle construct is targeted to bind to glut-1 by using a glut-1 antibody as a targeting agent.4. The method of claim 1 , wherein the therapeutically effective dosage of the composition comprises 6 mg/kg of curcumin.5. The method of claim 1 , wherein the therapeutically effective dosage of the composition comprises 1.5 mg/kg of doxorubicin.6. The method of claim 1 , wherein the composition further comprises a pharmaceutically acceptable carrier for intravenous administration.7. A pharmaceutical composition claim 1 , comprising:an inhibitor of NF-kB;a glut-1 antibody; anda pharmaceutically acceptable carrier.8. The pharmaceutical composition of claim 7 , wherein the inhibitor of NF-kB is an siRNA molecule.9. The pharmaceutical composition of claim 7 , wherein the glut-1 antibody is toxic.12. The pharmaceutical composition of claim 7 , further comprising a micelle.13. A method of treating a cancer in a subject claim 7 , comprising:providing a composition ...

Magnetic Nanoparticle-Polymer Complexes and uses Thereof

The present invention relates to magnetic nanoparticles coated with block copolymers. The invention further relates to methods of increasing cellular uptake of magnetic nanoparticles and use of the coated magnetic particles to selectively kill cancer cells, treat cancer, detect cancer, and for biomedical imaging. 1. A magnetic nanoparticle polymer complex (MNPC) comprising a magnetic nanoparticle coated with one or more polymers , such as a block copolymer , such as an amphiphilic block copolymer.23-. (canceled)4. The MNPC of claim 1 , wherein the at least one block copolymer comprises a polyacid block.5. The MNPC of claim 4 , wherein the polyacid block is polyacrylic acid or polymethacrylic acid.6. The MNPC of claim 1 , wherein the at least one block copolymer is polyacrylic acid-poloxamer.7. (canceled)8. The MNPC of claim 1 , wherein the at least one polymer is attached to the nanoparticle by a polyelectrolyte chain claim 1 , hydrophilic nonionic polymer claim 1 , or anchoring group claim 1 , such as by a covalent link.9. (canceled)10. The MNPC of claim 8 , wherein the polyelectrolyte chain is a polyanion or a polycation.11. (canceled)12. The MNPC of claim 8 , wherein the hydrophilic nonionic polymer is poly(ethylene oxide) claim 8 , poly(2-methyl-2-oxazoline) claim 8 , poly(2-ethyl-2-oxazoline claim 8 , or polysarcosine.13. The MNPC of claim 1 , wherein the nanoparticle is hydrophobically modified and non-covalently linked to a hydrophobic block of the at least one block copolymer.14. The MNPC of claim 1 , wherein the nanoparticle is non-covalently linked to a hydrophilic block of the at least one block copolymer.15. The MNPC of claim 1 , wherein the MNPC comprises a micelle formed by hydrophilic and hydrophobic blocks of the at least one block copolymer.16. (canceled)17. The MNPC of claim 1 , wherein the nanoparticle has a diameter of less than about 50 nm.18. (canceled)19. The MNPC of claim 1 , wherein the MNPC has a diameter of less than about 100 nm.20. The ...

Protein delivery to membranes

There is provided a phospholipid composition which is a bilayer or micelle comprising at least one embedded protein-polymer surfactant conjugate comprising an anchor protein, wherein the anchor protein is a cationised protein or an anionised protein, the composition characterised in that the anchor protein is: a) an active enzyme; orb) is a protein which does not comprise a —CH 2 C(O)NCH 3 (CH 2 ) 3 NCH 3 ) 2 H + linker covalently bonded to an amino acid side chain.

OLIGOLACTIC ACID CONJUGATES AND MICELLES WITH ENHANCED ANTICANCER EFFICACY

The present technology relates generally to oligolactic acid conjugates of paclitaxel, rapamycin, selumetinib, and other anticancer agents, micelle compositions containing such conjugates and methods of preparing and using such compositions to treat various cancers. Specifically, there are provided oligolactic acid conjugates wherein the oligolactic acid comprises 2 to 24 lactic acid subunits and is attached through an ester linkage to the oxygen of the 7-hydroxyl of the paclitaxel or paclitaxel derivative, the 40-hydroxyl of the rapamycin or rapamycin derivative, and the 2′-hydroxyl of the selumetinib or selumetinib derivative. Compositions comprising water and a micelle comprising a polylactic acid-containing polymer and the oligolactic acid conjugate may be readily prepared. Methods of inhibiting or killing cancer cells and treating paclitaxel, rapamycin, and/or selumetinib cancers are also provided. 158-. (canceled)59. An oligolactic acid conjugate selected from the group consisting of a 7-oligolactic acid conjugate of paclitaxel or a paclitaxel derivative , a 40-oligolactic acid conjugate of rapamycin or a rapamycin derivative , and a 2′-oligolactic acid conjugate of selumetinib or a selumetinib derivative.60. The oligolactic acid conjugate of claim 59 , wherein:the 7-oligolactic acid is attached through an ester linkage to the oxygen of the 7-hydroxyl of the paclitaxel or paclitaxel derivative;the 40-oligolactic acid is attached through an ester linkage to the oxygen of the 40-hydroxyl of the rapamycin or rapamycin derivative; andthe 2′-oligolactic acid is attached through an ester linkage to the oxygen of the 2′-hydroxyl of the selumetinib or selumetinib derivative.61. The oligolactic acid conjugate of comprising paclitaxel or docetaxel.62. The oligolactic acid conjugate of comprising rapamycin or everolimus.63. The oligolactic acid conjugate of comprising selumetinib claim 59 , binimetinib claim 59 , or GDC-0623.64. A composition comprising water and a ...

CORE-SHELL PARTICLES FOR CONTROLLED RELEASE

Compositions, methods, and systems for controlling crystallization of an agent are generally described. In some embodiments, an agent is crystallized in the presence of polymer matrices, such as polymer particles. The polymer matrix may influence at least a portion of the crystallization process and/or the resulting composition. In some such embodiments, the polymer matrix allows one or more aspect of the process and/or composition to be controlled and/or altered. For instance, the polymer matrix may act as a crystallization promoter and/or acceptable carriers of the crystallized agent. In certain embodiments, the polymer matrix described herein, can be used with any agent regardless of its chemical and/or physical properties. 1. A method comprising:forming an emulsion comprising a non-aqueous carrier containing a hydrophobic drug dispersed in an aqueous carrier, wherein the aqueous carrier comprises a first polymer, and wherein the emulsion further comprises poly(vinyl alcohol);at least partially cross-linking the first polymer by exposing it to a cross-linking agent;removing sufficient aqueous carrier and sufficient non-aqueous carrier, thereby crystallizing the drug as a dispersion of solid hydrophobic drug in a cross-linked matrix comprising the first polymer.2. A method comprising:forming an emulsion comprising a non-aqueous carrier containing a hydrophobic drug dispersed in an aqueous carrier, wherein the aqueous carrier comprises a first polymer, and wherein the emulsion further comprises a second polymer;at least partially cross-linking the first polymer by exposing it to a cross-linking agent;removing sufficient aqueous carrier and the non-aqueous carrier, thereby:crystallizing the drug as a dispersion of solid hydrophobic drug in a cross-linked matrix comprising the first polymer, andforming a composite core-shell particle, wherein the shell comprises the second polymer.3. A composite core-shell particle comprising:a core, which comprises a crystalline ...

COMPOSITIONS AND METHODS FOR DELIVERY OF RNA

The disclosure provides nanoemulsion compositions and methods of making and using thereof to deliver a bioactive agent such as a nucleic acid to a subject. The nanoemulsion composition comprises a hydrophobic core based on inorganic nanoparticles in a lipid nanoparticle that allows imaging as well as delivering nucleic acids. Methods of using these particles for treatment and vaccination are also provided. 1. A nanoemulsion composition comprising a plurality of nanoemulsion particles , wherein the plurality of nanoemulsion particles comprise:a hydrophobic core comprising a mixture of a liquid oil and a solid inorganic nanoparticle;a cationic lipid;a hydrophilic surfactant;a hydrophobic surfactant; anda nucleic acid, wherein the nucleic acid modulates innate immune response and is complexed with the nanoemulsion particles.2. The nanoemulsion composition of claim 1 , wherein the nucleic acid is RNA.3. The nanoernuision composition of claim 2 , wherein the RNA is double-stranded RNA.4. The nanoemulsion composition of claim 1 , wherein the nucleic acid is DNA.5. The nanoemulsion composition of claim 1 , wherein the nucleic acid is a TLR agonist.6. The nanoemulsion composition of claim 5 , wherein the TLR agonist is a TLR3.7. The nanoemulsion composition of claim 1 , wherein the nucleic acid is RIG-I agonist.8. The nanoemulsion composition of claim 1 , wherein the hydrophobic surfactant is selected from the group consisting of sorbitan monostearate claim 1 , sorbitan monooleate claim 1 , and sorbitan trioleate.9. The nanoemulsion composition of claim 1 , wherein cationic lipid is selected from the group consisting of 1 claim 1 ,2-dioleoyloxy-3-(trimethylammonium)propane (DOTAP); 3b-[N—(N′ claim 1 ,N′-dimethylaminoethane)-carbamoyl]cholesterol (DC Cholesterol); dimethyldioctadecylammonium (DDA); 1 claim 1 ,2-dimyristoyl-3-trimethylammoniumpropane (DMTAP) claim 1 , dipalmitoyl(C16:0)trimethyl ammonium propane (DPTAP); distearoyltrimethylammonium propane (DSTAP); N-[1-(2 ...

Method of treating cancer by using siRNA nanocomplexes

The present invention is related to a method for treating cancer by using siRNA nanocomplexes. The present nanocomplex consists of a nucleic acid molecule, a monocationic drug and a biocompatible polymer surfactant, and not only has a hydrodynamic size of 10 nm or less, but uniformly distributes as a colloidal form in an aqueous environment. In addition, the nanoscale colloidal formulation of the present invention could protect the nucleic acid molecule from a nuclease (for example, serum nucleases) rich in a physiological environment through the formulation of a stable monocomplex, and provide improvement of cell penetration and in vivo delivery via a micellar structure as well as further protection of the nucleic acid molecule by a micellar passivation. Therefore, the present nanocomplex and a composition and system using the same can deliver an active ingredient (for example, a nucleic acid molecule and monocationic drug) into a cell/tissue of interest in a stable manner, and may be effectively applied for treating or detecting diverse disorders (practically, cancers). 1. A method for treating cancer comprising the steps of: a) administrating a subject in need nanocomplex comprising a hydrophobically associated multiple monocomplex (HMplex) consisting of a nucleic acid molecule , a monocationic drug and a biocompatible polymer surfactant encapsulating the multiple monocomplex; b) measuring fluorescence in the cancer cells or tumor tissue of the subject.2. The method of claim 1 , wherein the nucleic acid molecule is selected from the siRNAs with 10 to 100 nucleotides and inhibits the expression of an oncogenic gene.3. The method of claim 2 , wherein the siRNAs inhibits the expression of a gene from the group of Bcl-2 claim 2 , Bcl-3 claim 2 , Bcl-4 claim 2 , Bcl-5 claim 2 , Bcl-6 claim 2 , HER2/Neu claim 2 , HER3 claim 2 , HER4 claim 2 , raf claim 2 , c-fos claim 2 , c-jun claim 2 , c-kit claim 2 , c-met claim 2 , c-ret claim 2 , hTERT claim 2 , and erbB.4. The ...

Vaccination composition

The present invention is directed to vaccination composition comprising a particle comprising a polymer matrix incorporating an adjuvant and/or an antigen, to method of making them and use. Particularly, the present invention results in adjuvants and/or antigens, covalently entrapped in or coupled to polymer carriers or polymeric devices, such as micelles, nanoparticles, microspheres and other types of polymer devices for controlled release; the adjuvant and/or antigen are covalently bonded in or to the polymer carriers or polymeric devices.

POLYMERSOMES FUNCTIONALISED WITH MULTIPLE LIGANDS

The present invention is directed to a nanoparticle or microparticle for binding to the surface of a cell, wherein the nanoparticle or microparticle comprises (i) multiple different ligand types on its external surface which are capable of binding to different respective receptor types on said cell surface, and (ii) a polymer brush on its external surface. The present invention is further directed to pharmaceutical compositions comprising a plurality of nanoparticles or microparticles of the invention, medical uses of such nanoparticles or microparticles, and a vaccine comprising such nanoparticles or microparticles. 1. A nanoparticle or microparticle for binding to the surface of a cell , wherein the nanoparticle or microparticle is a polymersome , liposome , synthosome or micelle that comprises at least a first ligand type on its external surface and at least a second ligand type on its external surface , wherein said first ligand type is capable of binding to a first receptor type on said cell surface , and said second ligand type is capable of binding to a second receptor type on said cell surface , further wherein the nanoparticle or microparticle comprises from 2 to 1000 ligands of the first ligand type and from 2 to 1000 ligands of the second ligand type , and wherein the nanoparticle or microparticle comprises a polymer brush on its external surface.2. A nanoparticle or microparticle according to claim 1 , wherein the nanoparticle or microparticle comprises a number of ligands of the first ligand type selected from the group consisting of: (a) from 5 to 1000 ligands of the first ligand type; and (b) from 10 to 500 ligands of the first ligand type.3. (canceled)4. A nanoparticle or microparticle according to claim 1 , wherein the nanoparticle or microparticle comprises from 20 to 200 ligands of the first ligand type.5. A nanoparticle or microparticle according to claim 1 , wherein the nanoparticle or microparticle comprises a number of ligands of the second ...

AMPHIPHILIC BLOCK COPOLYMERS, MICELLES, AND METHODS FOR TREATING OR PREVENTING HEART FAILURE

Micelle-forming amphiphilic block copolymers for use in targeting cardiac cells (e.g. fibrotic cells) of a subject suffering from heart failure, micelles containing the micelle-forming amphiphilic block copolymers together with a cardioactive agent, and related compositions and methods for treating or preventing heart failure, e.g. heart failure with preserved ejection fraction (HFpEF) also known as diastolic heart failure. 125-. (canceled)27. The method of claim 26 , wherein the micelle passively accumulates in cardiac fibroblasts.28. The method of claim 26 , wherein the cardioactive agent is selected from the group consisting of anti-fibrotic agents claim 26 , anti-inflammatory agents claim 26 , angiotensin receptor blockers claim 26 , inotropes claim 26 , angiotensin II converting enzyme (ACE) inhibitors claim 26 , cannabidiol claim 26 , calcium channel blockers claim 26 , cannabinoids claim 26 , anti-angiogenic agents claim 26 , vascular endothelial growth factor (VEGF) antagonists claim 26 , basic fibroblast growth factor (bFGF) antagonists claim 26 , bFGF receptor antagonists claim 26 , transforming growth factor-beta (TGF-β) antagonists claim 26 , TGF-β receptor antagonists claim 26 , steroidal anti-inflammatory agents claim 26 , tumor necrosis factor (TNF) antagonists claim 26 , VEGF claim 26 , bFGF claim 26 , TGF-beta claim 26 , VEGF receptor antagonists claim 26 , rapamycin claim 26 , amiodarone claim 26 , cyclosporine claim 26 , cyclosporine A claim 26 , dobutamine claim 26 , lipophilic derivatives thereof claim 26 , and combinations thereof.29. The method of claim 26 , wherein the cardioactive agent is cannabidiol.30. The method of claim 26 , wherein the amphiphilic block copolymer is selected from the group consisting of PEO-polycaprolactone claim 26 , PEO-poly(valerolactone) claim 26 , PEO-poly(butyrolactone)s claim 26 , PEO-polylactones claim 26 , PEO-poly lactides claim 26 , PEO-polyglycolides claim 26 , PEO-polylactide-glycolide claim 26 , PEO-poly( ...

OLIGOLACTIC ACID CONJUGATES AND MICELLES WITH ENHANCED ANTICANCER EFFICACY

The present technology relates generally to oligolactic acid conjugates of paclitaxel, rapamycin, selumetinib, and other anticancer agents, micelle compositions containing such conjugates and methods of preparing and using such compositions to treat various cancers. Specifically, there are provided oligolactic acid conjugates wherein the oligolactic acid comprises 2 to 24 lactic acid subunits and is attached through an ester linkage to the oxygen of the 7-hydroxyl of the paclitaxel or paclitaxel derivative, the 40-hydroxyl of the rapamycin or rapamycin derivative, and the 2′-hydroxyl of the selumetinib or selumetinib derivative. Compositions comprising water and a micelle comprising a polylactic acid-containing polymer and the oligolactic acid conjugate may be readily prepared. Methods of inhibiting or killing cancer cells and treating paclitaxel, rapamycin, and/or selumetinib cancers are also provided. 133-. (canceled)34. An oligolactic acid conjugate selected from the group consisting of a 7-oligolactic acid conjugate of paclitaxel or a paclitaxel derivative , a 40-oligolactic acid conjugate of rapamycin or a rapamycin derivative , and a 2′-oligolactic acid conjugate of selumetinib or a selumetinib derivative; the oligolactic acid comprises 2 to 24 lactic acid subunits;', 'the 7-oligolactic acid is attached through an ester linkage to the oxygen of the 7-hydroxyl of the paclitaxel or paclitaxel derivative;', 'the 40-oligolactic acid is attached through an ester linkage to the oxygen of the 40-hydroxyl of the rapamycin or rapamycin derivative; and', 'the 2′-oligolactic acid is attached through an ester linkage to the oxygen of the 2′-hydroxyl of the selumetinib or selumetinib derivative, 'wherein35. The oligolactic acid conjugate of wherein the oligolactic acid comprises 4 to 20 lactic acid subunits.36. The oligolactic acid conjugate of wherein the oligolactic acid comprises 6 to 18 lactic acid subunits.37. The oligolactic acid conjugate of comprising paclitaxel or ...

Compositions and methods for organ specific delivery of nucleic acids

The present disclosure provides compositions which shown preferential targeting or delivery of a nucleic acid composition to a particular organ. In some embodiments, the composition comprises a steroid or sterol, an ionizable cationic lipid, a phospholipid, a PEG lipid, and a permanently cationic lipid which may be used to deliver a nucleic acid.

COMPOSITIONS AND METHODS FOR RESTORING ENDOTHELIAL GLYCOCALYX

The present disclosure relates to compositions and methods for restoring endothelial glycocalyx. Exemplary compositions include nanoparticle compositions of preassembled glycocalyx. 1. A composition comprising: a proteoglycan , heparan sulfate , and hyaluronic acid , formulated as a nanoparticle.2. The composition of claim 1 , wherein the proteoglycan is selected from the group consisting of syndecan claim 1 , glypican claim 1 , perlecan claim 1 , versican claim 1 , decorin claim 1 , biglycan claim 1 , and mimecan.3. The composition of claim 2 , wherein the proteoglycan comprises syndecan-1 claim 2 , syndecan-2 claim 2 , syndecan-3 or syndecan-4 claim 2 , or mixtures thereof.4. The composition of claim 1 , further comprising an antibody for targeting the composition to the endothelial glycocalyx.5. The composition of claim 4 , wherein the antibody comprises anti-CD31 claim 4 , anti-CD117 (C-Kit) claim 4 , or anti-CD44 antibody.6. The composition of claim 1 , wherein the wherein the nanoparticle comprises micelles claim 1 , liposomes claim 1 , polymersomes claim 1 , hydrogel particles or polymer particles.7. The composition of claim 1 , wherein the nanoparticle has a maximum linear dimension of 1000 nanometers.8. The composition of claim 1 , further comprising a drug or active agent.9. The composition of claim 8 , wherein the active agent heparan sulfate is substituted with sulodexide.10. The composition of claim 6 , wherein the nanoparticle is a liposome and the liposome is optionally PEGylated.11. The composition of claim 3 , wherein the syndecan is labeled with a detectable label.12. The composition of claim 11 , wherein the electron microscopy detectable label is gold.13. A method for restoring endothelial glycocalyx in desired membranes in a patient in need thereof claim 1 , comprising administering an effective amount of the composition of to the patient.14. The method of claim 11 , wherein the composition further comprises CD44 which specifically targets the ...

POLY(BETA-AMINO ESTER)-CO-POLYETHYLENE GLYCOL (PEG-PBAE-PEG) POLYMERS FOR GENE AND DRUG DELIVERY

Polyethylene glycol (PEG)-b-poly(β-amino ester) (PBAE) co-polymers (PEG-PBAE) and blends of PEG-PBAEs and PBAEs and their use for delivering drugs, genes, and other pharmaceutical or therapeutic agents safely and effectively to different sites in the body and to different cells, such as cancer cells, are disclosed. 2. The PEG-PBAE co-polymer of claim 1 , wherein the PEG subunit has a molecular weight selected from the group consisting of about 0.5 kDa to about 5 kDa claim 1 , about 5 kDa to about 10 kDa claim 1 , about 10 kDa to about 20 kDa claim 1 , and about 20 kDa to about 30 kDa.3. The PEG-PBAE co-polymer of claim 1 , wherein the PBAE subunit has a molecular weight ranging from about 1 kDa to about 5 kDa claim 1 , 5 kDa to about 10 kDa claim 1 , about 4 kDa to about 13 kDa claim 1 , about 10 kDa to about 15 kDa claim 1 , about 15 kDa to about 25 kDa claim 1 , about 25 kDa to about 50 kDa claim 1 , and about 50 kDa to about 100 kDa.4. The PEG-PBAE co-polymer of claim 1 , wherein the co-polymer is selected from the group consisting of: PEG-B4S4-PEG claim 1 , PEG-B4S4-PEG claim 1 , PEG-B4S4-PEG claim 1 , and PEG-B4S4-PEG.5. A micelle comprising a polyethylene glycol (PEG)-b-poly(β-amino ester) (PBAE) co-polymer of .6. The micelle of claim 5 , further comprising a cargo.7. The micelle of claim 6 , wherein the cargo comprises one or more hydrophobic drugs.8. A particle comprising a blend of a polyethylene glycol (PEG)-b-poly(β-amino ester) (PBAE) co-polymer of Formula (I) and a poly(β-amino ester) (PBAE).9. The particle of claim 8 , wherein the poly(β-amino ester) (PBAE) comprises an unmodified poly(β-amino ester) (PBAE).10. The particle of claim 8 , further comprising a cargo.11. The particle of claim 10 , wherein the cargo comprises a drug or a gene.12. The particle of claim 11 , wherein the cargo comprises DNA or siRNA.17. The method of claim 13 , wherein the functionalized PEG molecule comprises PEG-SH.18. The method of claim 13 , wherein step (b) further ...

Thermally Stabilized Nanoemulsion

This invention describes of a means of stabilizing lipophilic drugs for long-term storage by incorporating them into a “thermally stabilized nanoemulsion” that has a phase transition temperature that is at or below the body temperature of 37 C and above a storage temperature of 4-8 C. One or more lipid soluble drugs are incorporated into the nanoemulsion at an elevated temperature above the phase transition temperature of the nanoemulsion and then stabilized for extended storage by lowering the temperature to below its phase transition temperature. This causes the nanoemulsion to transform into solid lipid nanospheres entrapping the drug within the solid lipid matrix. Upon rewarming the lipid nanospheres they will reconvert to an oil-in-water nanoemulsion suitable for administration to the patient in need. This invention further discloses disease targeting thermally stabilized nanoemulsions utilizing targeting agents such as antibodies, aptamers, binding peptides, hormones, cytokines and the like, attached to the exterior of the nanodroplets comprising the nanoemulsion. 1. A means of preparing a thermally stabilized nanoemulsion incorporating one or more lipid soluble therapeutic drugs , whereby the nanoemulsion has a phase transition temperature that is designed to be an oil-in-water nanoemulsion at body temperature; and which converts to a suspension of drug containing lipid nanospheres when the temperature is lowered to a value that is below body temperature.2. A means of preparing a disease targeting thermally stabilized nanoemulsion incorporating one or more lipid soluble therapeutic drugs , whereby the nanoemulsion has a phase transition temperature that is designed to be an oil-in-water nanoemulsion at body temperature; and which converts to a suspension of drug containing lipid nanospheres when the temperature is lowered to a value that is below body temperature; and where the disease targeting agent is attached to the exterior surface of nanodroplets ...

DENDRI-TAC AND THEIR USE AS THERANOSTICS

The present invention relates to novel amphiphilic dendrimers, hereafter denoted Dendri-TAC. The present invention also relates to perfluorocarbon nanoemulsions stabilized by these amphiphilic dendrimers and their uses for in vivo diagnostic and/or for therapy, notably as theranostic tools, for detection and/or treatment of cancer. 6. Dendrimer which is selected from:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'wherein x and w are as defined in .'}7. A nanoemulsion comprising:as a discontinuous phase, a perfluorocarbon compound,as a continuous phase, an aqueous phase,{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'an amphophilic dendrimer as defined in as a surfactant,'}optionally a biocompatible hydrocarbon oil.8. The nanoemulsion of claim 7 , wherein the discontinuous phase is loaded with solubilized oxygen.9. The nanoemulsion of claim 7 , wherein the discontinuous phase farther comprises a sonosensitive and/or photosensitive agent and/or an active ingredient.10. The nanoemulsion of claim 7 , wherein the discontinuous phase further comprises a sonosensitive and/or photosensitive agent and/or an active ingredient claim 7 , said nanoemulsion further comprising a biocompatible hydrocarbon oil12. A method of diagnosis or treatment comprising a step of administration to a patient in need thereof an effective amount of the nanoemulsion of .13. The method of claim 12 , in tumor imaging.14. The method of claim 13 , wherein the tumor imaging is selected from contrast echography claim 13 , near-infrared fluorescence claim 13 , photoacoustic imaging and Magnetic Resonance Imaging (MRI) claim 13 , in particular from ultrasound echography claim 13 , and fluorine Nuclear Magnetic Resonance.15. The method of claim 12 , in the treatment of cancer.16. The method of claim 15 , in sonodynamic or photodynamic therapy.17. The method of claim 12 , wherein the terminal group of the dendrimer comprises or is attached to a targeting ligand.18. The method of claim 17 , wherein the ...

Metap-2 inhibitor polymersomes for therapeutic administration

Described herein are MetAP-2 inhibitors and compositions and formulations thereof, and more particularly compositions and formulations of MetAP-2 inhibitors wherein the MetAP-2 inhibitor is associated with a block copolymer comprising a hydrophilic polymer moiety and a hydrophobic polymer moiety. The present invention also relates to compositions and formulations comprising MetAP-2 inhibitors for oral administration or administration via routes such as topical or ocular administration. The present invention also provides methods to treat conditions associated with or related to the over-expression or over-activity of MetAP-2 by administering the compositions and formulations comprising MetAP-2 inhibitors as disclosed herein.

BIODEGRADABLE THERMO-RESPONSIVE POLYMERS AND USES THEREOF

The invention provides for novel thermo-responsive polymers and compositions comprising the same. In some embodiments, the polymers are water soluble, pH-degradable and have tunable lower critical solution temperatures. Other aspects of the invention include micelles and gels comprising the thermo-responsive polymers and derivatives thereof, as well as methods of delivering therapeutic agents comprising administering a biodegradable gel or micelle comprising a polyacetal compound cross-linked with a linker. 4. The compound of claim 1 , wherein the value of [(m+m)/p] is a number between 0 and 8.5. The compound of claim 1 , wherein the compound has a lower critical solution temperature of about 6° C. to about 80° C.6. The compound of claim 5 , wherein the lower critical solution temperature is about 25° C. to about 45° C.79-. (canceled)10. The compound of claim 1 , wherein X is C-Cn-alkyl.11. The compound of claim 1 , wherein p is an integer between 3 and 50.1220-. (canceled)2225-. (canceled)26. The compound of claim 21 , wherein{'sub': '1', 'each nmay be the same or different and is an integer between 2 and 4;'}{'sub': '1', 'each mmay be the same or different and is an integer between 0 and 2;'}{'sub': 2', '5, 'each X may be the same or different and is C-Calkyl;'}{'sub': '2', 'each mmay be the same or different and is an integer between 0 and 3; and'}p is an integer between 3 and 100,2729-. (canceled)3185-. (canceled)86. A method for treating cancer in a subject the method comprising administering to a subject a therapeutic amount of the compound of claim 1 , wherein the cancer comprises breast cancer claim 1 , non-small cell lung cancer claim 1 , pancreatic cancer claim 1 , acute lymphoblastic leukemia (ALL) claim 1 , acute myeloid leukemia (AML) claim 1 , gastric cancer claim 1 , Hodgkin lymphoma claim 1 , neumblastoma claim 1 , non-Hodgkin lymphoma claim 1 , ovarian cancer claim 1 , small cell lung cancer claim 1 , soft tissue and bone sarcomas claim 1 , thyroid ...

PEGYLATED HEPARIN NANOMICELLE LOADED WITH CARBOXYLIC ACID ANTI-TUMOR DRUG AND PREPARATION METHOD THEREOF

The present invention discloses a PEGylated heparin nanomicelle loaded with a carboxylic acid anti-tumor drug. A drug loading system is a conjugate formed by loading the carboxylic acid anti-tumor drug onto a PEGylated heparin molecule. A natural polysaccharide heparin that is biodegradable, good in compatibility and high in availability is used as a drug carrier. By means of combining PEG modification and the carboxylic acid anti-tumor drug, nanoparticles show a remarkably enhanced anti-tumor therapeutic index and biological safety during in vivo treatment when compared with free drugs. 2. The PEGylated heparin nanomicelle loaded with the carboxylic acid anti-tumor drug according to claim 1 , characterized in that polyethylene glycol (PEG) is mPEG2000.3. The PEGylated heparin nanomicelle loaded with the carboxylic acid anti-tumor drug according to claim 1 , characterized in that the D group is connected with an aliphatic carboxyl group in the drug molecule via an ester bond.4. The PEGylated heparin nanomicelle loaded with the carboxylic acid anti-tumor drug according to claim 1 , characterized in that the carboxylic acid anti-tumor drug comprises pemetrexed claim 1 , pemetrexed disodium claim 1 , raltitrexed or bendamustine.6. The preparation method of the PEGylated heparin nanomicelle loaded with the carboxylic acid anti-tumor drug according to claim 5 , characterized in that in the reactions A claim 5 , B and C of step (1) claim 5 , a catalyst DIEA is added.7. The preparation method of the PEGylated heparin nanomicelle loaded with the carboxylic acid anti-tumor drug according to claim 5 , characterized in that in the reaction D claim 5 , enoxaparin sodium is dissolved in a MeS buffer solution and activated by addition of DMTMM claim 5 , then S-(2-aminoethylthio)-2-thiopyridine that is dissolved in the MeS buffer solution is added dropwise to the system for reaction claim 5 , to obtain the intermediate A.8. The preparation method of the PEGylated heparin ...

Compositions for treating drug resistant bacteria and biofilm

A broad-based remediation mechanism against MRFs and alternative fecal indicators such as multidrug resistant Pseudomonas aeruginosa , including nanotechnology formulations and methodologies that may be used to develop novel mitigation strategies against certain drug resistant bacterial strains. The current invention relates to mitigation of drug resistant bacteria, for example in hospitals and in food animals, and to the identification. The invention uses hybrid nanomaterials comprising oligo-chitosan and zinc oxide formulated as nanoparticles and micelles. The invention also relates to the treatment of multi-drug resistant biofilms which mimic in vivo conditions. The inventors unexpectedly found unique properties of very small oligomers of chitosan that effectively mitigate MRF and alternative resistant strain-induced illnesses without compromising the balance of the beneficial flora in the physiological and ecological microenvironments. The combination of chitosan with zinc oxide demonstrated synergistic and unexpected effects in treating multi-drug resistant pathogens.

MACROMOLECULAR CHEMOTHERAPEUTICS

Embodiments of the invention are directed to a macromolecular chemotherapeutic. A non-limiting example of the macromolecular chemotherapeutic includes a block copolymer. The block copolymer can include a water-soluble block, a cationic block, and a linker, wherein the linker is connected to the water-soluble bock and the charged block. 1. A macromolecular chemotherapeutic , comprising: a water-soluble block,', 'a cationic block, and', 'a linker, wherein the linker is connected to the water-soluble bock and the charged block., 'a block copolymer comprising2. The macromolecular chemotherapeutic of claim 1 , wherein the water-soluble block comprises polyethylene oxide.3. The macromolecular chemotherapeutic of claim 1 , wherein the linker is a cleavable linker.4. The macromolecular chemotherapeutic of claim 3 , wherein the cleavable linker comprises an acetal or a disulfide.5. The macromolecular chemotherapeutic of claim 3 , wherein the polyethylene glycol has an average molecular weight of 2000 to 20 claim 3 ,000 daltons.6. The macromolecular chemotherapeutic of claim 1 , wherein the cationic block includes polymeric subunit comprising a polycarbonate backbone having from 4 to 8 atoms.8. The macromolecular chemotherapeutic of claim 1 , wherein the block copolymer is self-immolative at a pH less than or equal to 6.5.9. A pharmaceutical composition claim 1 , comprising: a water-soluble block,', 'a cationic block, and', 'a linker, wherein the linker is connected to the water-soluble bock and the charged block; and', 'a solvent., 'a block copolymer comprising10. The pharmaceutical composition according to further comprising a plurality of micelles.11. The pharmaceutical composition according to claim 10 , wherein the micelles are mixed micelles.12. The pharmaceutical composition according to claim 10 , wherein the micelles have an average diameter of 20 to 200 nanometers.13. The pharmaceutical composition according to claim 10 , wherein the water-soluble block comprises ...

PRESERVATIVE FREE OCULAR COMPOSITIONS AND METHODS FOR USING THE SAME FOR TREATING DRY EYE DISEASE AND OTHER EYE DISORDERS

The present invention provides a preservative free ophthalmic formulation. In particular, the ophthalmic formulations of the invention are aqueous formulations comprising nanoemulsion of oil. The present invention also provides a method for treating an eye disorder. In one particular embodiment, the invention provides methods for treating dry eye syndrome using an preservative free formulation comprising a nanoemulsion of oil and alpha 2 adrenergic agonist, pharmaceutically acceptable salt thereof or a mixture thereof. In particular, the alpha 2 adrenergic agonist of the invention has a higher alpha 2A agonist activity compared to alpha 2B agonist activity. This invention also provides a preservative free ophthalmic composition comprising a nanoemulsion of oil, a therapeutically effective amount of an alpha 2 adrenergic agonist, a pharmaceutically acceptable salt thereof or a combination thereof as an active ingredient for treating a dry eye syndrome. 1. A preservative free aqueous ophthalmic solution comprising:(a) an alpha 2 adrenergic agonist, a pharmaceutically acceptable salt thereof, or a combination thereof;(b) a nanoemulsion of oil;(c) a pharmaceutically acceptable excipient; and(d) water.2. The preservative free aqueous ophthalmic solution of claim 1 , wherein said alpha 2 adrenergic agonist has a higher alpha 2A agonist activity compared to alpha 2B agonist activity.3. The preservative free aqueous ophthalmic solution of claim 1 , wherein said pharmaceutically acceptable excipient is selected from the group consisting of: a crosslinking agent claim 1 , a surfactant claim 1 , gum claim 1 , a resin claim 1 , a pH adjuster claim 1 , a stabilizer claim 1 , an antioxidant claim 1 , an ultraviolet absorbent claim 1 , a wetting agent claim 1 , and a combination thereof.4. The preservative free aqueous ophthalmic solution of claim 3 , wherein said pharmaceutically acceptable excipient comprises polysorbate 80 claim 3 , poloxamer claim 3 , tylaxopol claim 3 , ...

CAPSULE FOR DRUG DELIVERY SYSTEMS OF TARGETED TISSUE-SPECIFIC DELIVERY TYPE USING CARBOSILANE DENDRIMER

The present invention relates to a targeting-type capsule for drug delivery systems. The present invention addresses the problem of providing a capsule for drug delivery systems by utilizing the reactivity of a thiol with an alkyl halide, wherein the capsule comprises a silole-containing carbosilane dendrimer and a labeling protein containing a target recognition site (e.g., green fluorescent protein), can include a biological polymer or another molecule therein, and can deliver the biological polymer or the like selectively into a target cell. 110-. (canceled)12. The endocytosis enhancing agent according to the claim 11 , wherein the capsule has the diameter from 50 to 500 nm size.13. The endocytosis enhancing agent according to the claim 11 , wherein said aqueous solvent is saline claim 11 , phosphate buffered saline claim 11 , Tris-HCl buffer claim 11 , HEPES buffer claim 11 , sodium citrate buffer claim 11 , and carbonate-bicarbonate buffer.14. The endocytosis enhancing agent according to the claim 11 , wherein said peptide has both functions to deliver the capsule to a tissue specifically claim 11 , and to improve the incorporation the delivered capsule into the cell of the cells; said peptide specifically bounds to the target protein selected from the group consisting of a surface antigen claim 11 , receptor claim 11 , gate claim 11 , transporter and channel claim 11 , all of them are expressed on the target tissue.17. The endocytosis enhancing agent according to the claim 11 , wherein said target tissue is any one of tissue selected from the group consisting of the normal tissue having inflammation claim 11 , the tissue including the cells having undesirable gene expressions claim 11 , the tissue composed of the cells having undesirable gene expressions claim 11 , and the tissue composed of tumor cells19. The endocytosis enhancing agent according to the claim 18 , wherein said fluorescent protein is any one of selected from the group consisting of red ...

NANOPARTICLES COMPRISING PROTEIN-POLYNUCLEOTIDE COMPLEXES AND FOR DELIVERING PROTEIN BASED COMPLEXES

This invention provides nanoparticles containing protein-polynucleotide complexes and methods of manufacture and methods of their use. These particles, when administered to a subject in need, are capable of delivering these complexes to target cells and target intracellular locations where they can perform a therapeutic function. In some embodiments, this therapeutic function includes gene editing, induction of gene skipping, and regulation of gene expression. The instant nanoparticles are generally formed by designing and synthesizing the polynucleotide to according to its intended function, combining it with a protein selected for its substrate specificity and enzymatic function in a manner to form a polynucleotide-protein complex, encapsulating the complexes by dispersion into a water-insoluble surfactant system, optionally adding a targeting ligand, and stabilizing the nanoparticles by crystallization of the ligand to the surface of the nanoparticles. 1. A composition comprising nanoparticles comprising a polynucleotide component , a protein component , a surfactant having an HLB value of less than 6.0 units , optionally a hydrophilic polymer , and optionally Li and Cs , wherein:a) the protein component and the polynucleotide component are capable of functioning together in a biologic system as a biologic agent;b) the protein component and the polynucleotide component form a complex;c) the complex and the surfactant form a surfactant micelle core;d) the optionally hydrophilic polymer, if present, forms a shell around the micelle core;e) the nanoparticles have an average diameter of less than about 50 nanometers, andf) the biologic agent is optionally a therapeutic agent.2. The composition of wherein the biologic agent is a RISC or a sgRNA-Cas complex.3. The composition of wherein the biologic agent is a PNA claim 1 , or an SGN.4. The composition of wherein the protein component is a RISC associated protein and the polynucleotide component is a guide strand and ...

MICELLIC ASSEMBLIES

Provided herein are micellic assemblies comprising a plurality of copolymers. In certain instances, micellic assemblies provided herein are pH sensitive particles. 120-. (canceled)22. The micelle-like assembly of claim 21 , wherein Qis a polyethylene glycol group.23. The micelle-like assembly of claim 21 , wherein the micelle-like assembly comprises at least one therapeutic agent.24. The micelle-like assembly of claim 23 , wherein the micelle-like assembly comprises a core and a shell claim 23 , wherein the therapeutic agent is in the shell of the micelle-like assembly.25. The micelle-like assembly of claim 24 , wherein the therapeutic agent is associated with the copolymer.26. The micelle-like assembly of claim 25 , wherein the therapeutic agent is ionically associated with the copolymer.27. The micelle-like assembly of claim 24 , wherein the therapeutic agent is a polynucleotide claim 24 , an oligonucleotide claim 24 , a gene expression modulator claim 24 , a knockdown agent claim 24 , an siRNA claim 24 , an RNAi agent claim 24 , a dicer substrate claim 24 , an miRNA claim 24 , an shRNA claim 24 , an antisense oligonucleotide claim 24 , or an aptamer.28. The micelle-like assembly of claim 24 , wherein the therapeutic agent is an siRNA.29. The micelle-like assembly of claim 21 , wherein v is from about 1 to about 25 kDa.30. The micelle-like assembly of claim 21 , wherein w is from about 1 to about 50 kDa.31. The micelle-like assembly of claim 21 , wherein v is from about 5 to about 25 kDa.32. The micelle-like assembly of claim 21 , wherein w is from about 5 to about 50 kDa.33. The micelle-like assembly of claim 21 , wherein the ratio of w to v is from 5:1 to 1:1.34. The micelle-like assembly of claim 21 , wherein Qis a residue selected from the group consisting of amino claim 21 , alkylamino claim 21 , ammonium claim 21 , alkylammonium claim 21 , guanidine claim 21 , imidazolyl claim 21 , pyridyl claim 21 , carboxyl claim 21 , sulfonamide claim 21 , boronate claim ...

SiRNA Phospholipid Conjugate

siRNA-conjugated liposomes and micelles, methods of making such conjugates, and methods of using such conjugates, such as for the delivery of siRNA to cells to reduce expression of target polypeptides in such cells, are described.

Self-manageable abnormal scar treatment with spherical nucleic acid (sna) technology

The disclosure is related to compositions and methods comprising spherical nucleic acids (SNAs) and their use in penetrating skin and inhibiting gene expression to develop a scar treatment.

NANODROPLET COMPOSITIONS FOR THE EFFICIENT DELIVERY OF ANTI-CANCER AGENTS

Disclosed herein are nanodroplet compositions composed of a copolymer with a hydrophilic block and a hydrophobic block, a poloxamer, an oil, an anti¬cancer agent, and optionally a lyoprotectant. The nanodroplet compositions exhibit low toxicity and are biodegradable, provide for slow, sustained release of the anti-cancer agent at tumor sites, and result in a greater reduction of tumor volume when administered to subjects with cancer as compared to several commercially-available products. Furthermore, the nanodroplet compositions can be imaged and their progress through the body tracked with magnetic resonance spectroscopy or ultrasound. 1. Nanodroplets comprising{'smallcaps': 'D,L', '(a) a copolymer comprising a hydrophilic block and a hydrophobic block, wherein the hydrophilic block of the copolymer is polyethylene glycol or monomethoxy polyethylene glycol, and the hydrophobic block of the copolymer is polylactide, a copolymer of lactide and glycolide, a copolymer of -lactide and glycolide, a polycaprolactone, a polyanhydride, or a polyorthoester;'}(b) a poloxamer,(c) an oil, and(d) an anti-cancer agent.2. The nanodroplets of claim 1 , wherein the copolymer is an A-B diblock copolymer claim 1 , wherein A is the hydrophilic block and B is the hydrophobic block.3. The nanodroplets of claim 1 , wherein the hydrophilic block has a molecular weight from 1 claim 1 ,000 Da to 3 claim 1 ,000 Da.4. The nanodroplets of claim 1 , wherein the hydrophilic block of the copolymer is monomethoxy polyethylene glycol having a molecular weight from 1 claim 1 ,500 Da to 2 claim 1 ,500 Da.5. The nanodroplets of claim 1 , wherein the hydrophobic block of the copolymer is polylactide.6. The nanodroplets of claim 1 , wherein the hydrophobic block of the copolymer is poly(-lactide).7. The nanodroplets of claim 1 , wherein the hydrophobic block has a molecular weight from 1 claim 1 ,000 Da to 3 claim 1 ,000 Da.8. The nanodroplets of claim 1 , wherein the hydrophobic block of the copolymer ...

Novel block copolymer and micelle compositions and methods of use thereof

Provided herein are block copolymers comprising a hydrophilic polymer segment and a hydrophobic polymer segment, wherein the hydrophilic polymer segment comprises a polymer selected from the group consisting of: poly(ethylene oxide) (PEO), poly(methacrylate phosphatidyl choline) (MPC), and polyvinylpyrrolidone (PVP), wherein the hydrophobic polymer segment comprises wherein R′ is —H or —CH 3 , wherein R is —NR 1 R 2 , wherein R 1 and R 2 are alkyl groups, wherein R 1 and R 2 are the same or different, wherein R 1 and R 2 together have from 5 to 16 carbons, wherein R 1 and R 2 may optionally join to form a ring, wherein n is 1 to about 10, and wherein x is about 20 to about 200 in total. Also provided are pH-sensitive micelle compositions for therapeutic and diagnostic applications.

BLOCK COPOLYMERS AND SELF-ASSEMBLING NANOPARTICLES FORMED THEREFROM

The subject matter of this invention relates to block copolymers (BCPs) and, more particularly, to block copolymers capable of self-assembly into nanoparticles for the delivery of hydrophobic cargos. The BCPs include a hydrophobic block that contains a thioether functional group that is susceptible to oxidation, transforming the solubility of the block from hydrophobic to hydrophilic, thereby releasing the hydrophobic cargo of the nanoparticle. 24-. (canceled)5. The block copolymer of claim 1 , capable of self-assembly into a nanoparticle in which the hydrophobic block forms a core of the nanoparticle and the hydrophilic block forms a shell of the nanoparticle.6. (canceled)1225-. (canceled)26. A micellar particle comprising:a hydrophilic shell; anda hydrophobic core within the hydrophilic shell,{'claim-ref': {'@idref': 'CLM-00005', 'claim 5'}, 'the hydrophilic shell and the hydrophobic core formed from the nanoparticle of .'}27. The block copolymer of claim 7 , capable of self-assembly into a nanoparticle in which the hydrophobic block forms a core of the nanoparticle and the hydrophilic block forms a shell of the nanoparticle.28. A micellar particle comprising:a hydrophilic shell; anda hydrophobic core within the hydrophilic shell,{'claim-ref': {'@idref': 'CLM-00027', 'claim 27'}, 'the hydrophilic shell and the hydrophobic core formed from the nanoparticle of .'}29. The block copolymer of claim 8 , capable of self-assembly into a nanoparticle in which the hydrophobic block forms a core of the nanoparticle and the hydrophilic block forms a shell of the nanoparticle.30. A micellar particle comprising:a hydrophilic shell; anda hydrophobic core within the hydrophilic shell,{'claim-ref': {'@idref': 'CLM-00029', 'claim 29'}, 'the hydrophilic shell and the hydrophobic core formed from the nanoparticle of .'}31. The block copolymer of claim 9 , capable of self-assembly into a nanoparticle in which the hydrophobic block forms a core of the nanoparticle and the hydrophilic ...

CONJUGATED LIPOMERS AND USES THEREOF

The present invention provides inventive conjugated polyethyleneimine (PEI) polymers and conjugated aza-macrocycles (collectively referred to herein as “conjugated lipomers” or “lipomers”) containing one or more groups of the formula (iii): 121-. (canceled)23. The conjugated lipomer of claim 22 , wherein each instance of Ris independently hydrogen or a group of the formula (iii′).24. The conjugated lipomer of claim 22 , wherein each instance of Ris independently substituted or unsubstituted alkyl; substituted or unsubstituted heteroalkyl; or a hydrophilic polymer.2528-. (canceled)29. The conjugated lipomer of claim 22 , wherein the dashed curved line claim 22 , together with G and Y claim 22 , is a covalent bond.32. The conjugated lipomer of claim 22 , wherein the lipomer comprises at least one instance of the group of the formula (vi).34. The conjugated lipomer of claim 22 , wherein the lipomer comprises at least one instance of the group of the formula (vii) claim 22 , (viii) claim 22 , or (ix).38. A composition comprising one or more conjugated lipomers of claim 22 , and claim 22 , optionally claim 22 , an excipient.39. The composition of claim 38 , wherein the composition is a pharmaceutical composition or a cosmetic composition.40. The composition of claim 38 , wherein the composition further comprises an agent.41. The composition of claim 40 , wherein the agent is an organic molecule claim 40 , inorganic molecule claim 40 , nucleic acid claim 40 , protein claim 40 , peptide claim 40 , polynucleotide claim 40 , targeting agent claim 40 , an isotopically labeled chemical compound claim 40 , vaccine claim 40 , or an immunological agent.42. The composition of claim 41 , wherein the agent is a polynucleotide claim 41 , and the polynucleotide is DNA or RNA.43. The composition of claim 42 , wherein the RNA is RNAi claim 42 , dsRNA claim 42 , siRNA claim 42 , shRNA claim 42 , miRNA claim 42 , or antisense RNA.4449-. (canceled)5153-. (canceled)54. A method of treating ...

NANOPARTICLE CONJUGATED SYNTHETIC OPIOID PRODRUGS AND METHODS OF THEIR USES

Provided herein are nanoparticle conjugated synthetic opioid prodrugs that target the peripheral mu opioid receptor (MOR). The prodrugs exhibit long-lived bioavailability, do not compromise the analgesic effects of opioids administered for pain relief (and in some cases can be used for pain relief), and do not induce opioid withdrawal symptoms, when their use is discontinued. Certain of the prodrugs are especially useful for the prevention and/or treatment of unwanted opioid-induced side effects such as opioid-induced constipation (OIC). 12. The method of claim 11 , wherein the substance addiction is selected from the group consisting of: opioid addiction claim 11 , cocaine addiction claim 11 , alcohol addiction claim 11 , amphetamine addiction claim 11 , methamphetamine addiction and bath salt addiction.13. The method of claim 12 , wherein the opioid addiction is heroin addiction claim 12 , morphine addiction claim 12 , oxycodone addiction or methadone addiction.14. The method of claim 11 , wherein the psychological brain disorder is selected from the group consisting of such as depression claim 11 , schizophrenia claim 11 , bipolar disorder claim 11 , schizoaffective disorder and gambling addiction.15. A method of producing an opioid prodrug claim 11 , comprisingreacting a free-base form of an opioid with polyethylene glycol (PEG) azide under conditions suitable to form an opioid-PEG-azide conjugate;performing ring-opening polymerization of acetylene-functionalized 3-ethyl-3-(hydroxymethyl)oxetane (EAMO) monomers under conditions suitable to generate back bones of polymerized EAMO [P(EAMO)]; andreacting the P(EAMO) with the opioid-PEG-azide conjugate via a click reaction under conditions suitable to form a P(EAMO)-opioid-PEG conjugate.16. The method of claim 15 , wherein the opioid is 17-cyclopropylmethyl-3 claim 15 ,14 β-dihydroxy-4 claim 15 ,5 α-epoxy-6β-[(4-pyridyl)acetamido]morphinan (NAP). This application claims benefit of U.S. provisional patent application ...

Multifunctional micellar nanoparticle-based drug and targeting agent system

Embodiments provide systems, methods, and compositions for nanoparticle-based drug delivery to target cells or tissues. A drug delivery system may include a nanoparticle with a targeting component and a therapeutic component. The nanoparticle may have a predetermined number or valence of targeting molecules for multivalent interaction with a target cell or tissue. Binding of the targeting molecules to the target cell may result in receptor-mediated uptake of the nanoparticle by the target cell. The therapeutic component may be subsequently released within an endocytic vesicle of the target cell. Nanoparticle-based drug delivery systems as described herein may provide improved efficacy and/or reduced toxicity.

MEMBRANE-LYTIC BLOCK COPOLYMERS

Membrane-lytic block copolymers, micellar assemblies, pharmaceutical compositions, and related methods are described. 2. The block copolymer of claim 1 , wherein A claim 1 , Aor Aindependently comprise repeating units selected from the group consisting of 2-(dimethylamino)ethyl methacrylate claim 1 , 2-dimethylaminoethyl acrylate claim 1 , (3-acrylamidopropyl)trimethylammonium chloride claim 1 , N-(3-aminopropyl) methacrylamide claim 1 , N claim 1 ,N-diethylacrylamide claim 1 , N claim 1 ,N-diethylmethacrylamide claim 1 , N claim 1 ,N-dimethylacrylamide claim 1 , N-[3-(dimethylamino)propyl]methacrylamide claim 1 , 2-aminoethyl methacrylate claim 1 , 2-(diethylamino)ethyl methacrylate claim 1 , 2-(dimethylamino)ethylmethacrylate claim 1 , [2-hydroxy-3-(2-aminoethyl) amino]propyl methacrylate claim 1 , [3methacryloylamino)propyl]trimethylammonium chloride claim 1 , and L-lysine.3. The block copolymer of claim 1 , wherein A claim 1 , Aor Aindependently comprise repeating units selected from the group consisting of methacrylic acid claim 1 , acrylic acid claim 1 , dimethylmaleic anhydride modified N-(3-aminopropyl) methacrylamide claim 1 , and 2-aminoethyl methacrylate.4. The block copolymer of claim 1 , wherein A claim 1 , Aor Aindependently comprise repeating units selected from the group consisting of oligo(ethylene glycol) claim 1 , hydroxypropylmethacrylamide claim 1 , 2-hydroxyethyl methacrylate claim 1 , N-isopropylacrylamide claim 1 , 3-glucanoamidopropyl methacrylamide claim 1 , 2-lactobionamidoethyl methacrylamide claim 1 , betaine claim 1 , phosphocholine claim 1 , sulfobetaine and carboxybetaine.5. The block copolymer of claim 1 , wherein A claim 1 , Aor Aindependently comprise repeating units selected from the group consisting of 2-diisopropylaminoethyl methacrylate claim 1 , 2-(pentamethyleneimino)ethyl methacrylate claim 1 , 2-(hexamethyleneimino)ethyl methacrylate claim 1 , 2-(dipropylamino) ethyl methacrylate claim 1 , 2-(dibutylamino) ethyl ...

LONG-CIRCULATING ZWITTERIONIC POLYPLEXES FOR siRNA DELIVERY

Provided herein are a polymer, a polyplex, and a method of treating a disease. The polymer includes a core-forming block and a zwitterionic corona block. The polyplex includes the polymer complexed with an active agent. The method of treating a disease comprises administering the polyplex to a subject in need thereof. 1. A polymer comprising:a core-forming block; anda zwitterionic corona block.2. The polymer of claim 1 , wherein the polymer is a diblock copolymer.3. The polymer of claim 1 , wherein the core-forming block includes a cationic component and a hydrophobic component.4. The polymer of claim 3 , wherein the cationic component and the hydrophobic component are at a ratio of between about 90:10 and 10:90.5. The polymer of claim 3 , wherein the cationic component is selected from the group consisting of diethyl amino ethyl methacrylate and dimethyl amino ethyl methacrylate (DMAEMA).6. The polymer of claim 3 , wherein the hydrophobic component is selected from the group consisting of poly(propylene sulfide) and butyl methacrylate (BMA).7. The polymer of claim 3 , wherein the core-forming block includes a random copolymer of dimethyl amino ethyl methacrylate (DMAEMA) and butyl methacrylate (BMA).8. The polymer of claim 1 , wherein the zwitterionic corona block includes at least one zwitterionic monomer.9. The polymer of claim 8 , wherein the zwitterionic monomer is selected from the group consisting of methacryloyloxyethyl phosphorylcholine (MPC) claim 8 , sulfobetaines claim 8 , phosphobetaines claim 8 , carboxybetaines claim 8 , and combinations thereof.10. The polymer of claim 9 , wherein the at least one zwitterionic monomer is methacryloyloxyethyl phosphorylcholine (MPC)11. A polyplex comprising a polymer according to complexed with an active agent.12. The polyplex of claim 11 , wherein the active agent is a short oligonucleotide.13. The polyplex of claim 11 , wherein the active agent is a siRNA.14. The polyplex of claim 11 , wherein the active agent is ...

NANO-FIBULAR NANOPARTICLE POLYMER-DRUG CONJUGATE FOR SUSTAINED DERMAL DELIVERY OF RETINOIDS

Disclosed herein are conjugated polymers comprising a polymer and an all-trans retinoic acid (ATRA) prodrug covalently bound to the polymer by a hydrolysable linker L or a pharmaceutically acceptable salt thereof, and methods of using same to treat certain disorders. In an embodiment, the conjugated polymer comprises poly (vinyl alcohol) covalently bound to ATRA through an ester linkage. 2. The conjugated polymer of claim 1 , wherein L is a moiety selected from —C(O)O— claim 1 , —OC(O)— claim 1 , —NR*C(O)— claim 1 , —C(O)NR*— claim 1 , —(C═N—N(R*))— claim 1 , —OC(O)NR*— claim 1 , —NR*C(O)O— claim 1 , —OC(O)NR*NR*— claim 1 , and —O—; wherein R* claim 1 , for each occurrence independently claim 1 , is hydrogen or a C1-C4 alkyl.3. The conjugated polymer of any one of or claim 1 , wherein:{'sup': 1', 'A', 'A', 'A', 'A', 'A', 'A', 'A, 'sub': 2', '2, 'each Rindependently is a halogen, R, —OR, —SR, —N(R), —COOR, —OC(O)R, wherein Ris, for each occurrence independently, hydrogen or a C1-C6 alkyl, optionally substituted with one or more groups selected from —OH, —NH, and —COOH; and'}{'sup': 2', '3', '4', 'B', 'B', 'B', 'B', 'B', 'B', 'B', 'B', 'B, 'sub': 2', '2', '2, 'R, R, and R, each independently, is —OH, —SH, —NH, —NHR, —COOH, R, —OR, —SR, —N(R), —COOR, —OC(O)R, —C(O)R, wherein Ris, for each occurrence independently a C1-C6 alkyl optionally substituted with one or more groups selected from —OH, —NH, and —COOH.'}4. The conjugated polymer of any one of to claim 1 , wherein L is a moiety selected from —C(O)O— claim 1 , —OC(O)— claim 1 , —NR*C(O)— claim 1 , or —C(O)NR*—.10. The conjugated polymer of claim 9 , wherein the polymer functionalization is from about 10% to about 50%.11. The conjugated polymer of claim 10 , wherein the polymer functionalization is 10%.12. A pharmaceutical composition claim 10 , comprising:{'claim-ref': [{'@idref': 'CLM-00001', 'claims 1'}, {'@idref': 'CLM-00011', '11'}], 'a conjugated polymer of any one of - in pharmaceutically acceptable carrier.'} ...

METHODS OF TREATING COLON CANCER USING NANOPARTICLE MTOR INHIBITOR COMBINATION THERAPY

The present application provides methods of treating a colon cancer (such as advanced and/or metastatic colon cancer) in an individual, comprising administering to the individual: a) an effective amount of a composition comprising nanoparticles comprising an mTOR inhibitor (such as a limus drug, such as sirolimus or a derivative thereof) and an albumin, b) an effective amount of anti-VEGF antibody (such as bevacizumab), and c) a therapeutically effective FOLFOX regimen (such as FOLFOX4 or a modified FOLFOX6). 1. A method of treating a colon cancer in an individual , comprising administering to the individual: a) an effective amount of a composition comprising nanoparticles comprising an mTOR inhibitor and an albumin , b) an effective amount of anti-VEGF antibody , c) a therapeutically effective FOLFOX regimen.2. The method of claim 1 , wherein the colon cancer comprises an mTOR-activation aberration.3. The method of claim 2 , wherein the mTOR-activation aberration comprises a PTEN aberration.4. The method of claim 1 , wherein the mTOR inhibitor is a limus drug.5. The method of claim 4 , wherein the limus drug is rapamycin.6. The method of claim 1 , wherein the anti-VEGF antibody is bevacizumab.7. The method of claim 1 , wherein the amount of the mTOR inhibitor in the mTOR inhibitor nanoparticle composition is from about 10 mg/mto about 30 mg/m.8. The method of claim 1 , wherein the mTOR inhibitor nanoparticle composition is administered weekly claim 1 , once every 2 weeks claim 1 , or once every 3 weeks.9. The method of claim 1 , wherein the average diameter of the nanoparticles in the composition is no greater than about 200 nm.10. The method of claim 1 , wherein the weight ratio of the albumin to the mTOR inhibitor in the nanoparticle composition is no greater than about 9:1.11. The method of claim 1 , wherein the nanoparticles comprise the mTOR inhibitor coated with the albumin.12. The method of claim 1 , wherein the mTOR inhibitor nanoparticle composition is ...

PATTERNED DOSING OF IMMUNOSUPPRESSANTS COUPLED TO SYNTHETIC NANOCARRIERS

Provided herein are methods and related compositions for administering viral vectors and synthetic nanocarriers comprising an immunosuppressant. In some embodiments, the methods and compositions provided herein achieve improved transgene expression and/or immune response reduction, such as downregulated IgM and/or IgG immune responses. 1. A method comprising:coadministering synthetic nanocarriers comprising an immunosuppressant and a viral vector to a subject, andadministering at least one pre-dose and/or at least one post-dose of the synthetic nanocarriers comprising an immunosuppressant without the viral vector to the subject.2. The method of claim 1 , wherein at least one pre-dose and at least one post-dose is administered to the subject.3. The method of claim 1 , wherein at least two pre-doses are administered to the subject.4. The method of claim 1 , wherein at least two post-doses are administered to the subject.5. The method of claim 1 , wherein the coadministering is repeated in the subject.6. The method of claim 5 , wherein at least one pre-dose and/or at least one post-dose of the synthetic nanocarriers comprising an immunosuppressant without the viral vector is administered to the subject with each repeated coadministering step.7. The method of claim 6 , wherein at least one pre-dose and at least one post-dose is administered to the subject with each repeated coadministering step.8. The method of claim 6 , wherein at least two pre-doses are administered to the subject with each repeated coadministering step.9. The method of claim 6 , wherein at least two post-doses are administered to the subject with each repeated coadministering step.10. The method of claim 1 , wherein administration of the pre-dose(s) and/or post-dose(s) occurs within 1 month prior or subsequent to claim 1 , respectively claim 1 , a coadministration.11. The method of claim 10 , wherein administration of the pre-dose(s) and/or post-dose(s) occurs within 2 weeks prior or subsequent to ...

Nanoparticle-based drug delivery

Embodiments provide systems, methods, and compositions for nanoparticle-based drug delivery to target cells or tissues. A drug delivery system may include a nanoparticle with a targeting component and a therapeutic component. The nanoparticle may have a predetermined number or valence of targeting molecules for multivalent interaction with a target cell or tissue. Binding of the targeting molecules to the target cell may result in receptor-mediated uptake of the nanoparticle by the target cell. The therapeutic component may be subsequently released within an endocytic vesicle of the target cell. Nanoparticle-based drug delivery systems as described herein may provide improved efficacy and/or reduced toxicity.

MULTI-FUNCTIONAL PARTICLES AND METHODS OF USING THE SAME

Provided herein are multi-functional particles. The particles may include poly(lactide-co-glycolide)-g-polyethylenimine (PLGA-g-PEI (PgP)), at least one targeting moiety, at least one therapeutic agent, and/or at least one nucleic acid. Also provided herein are methods of using the multi-functional particles. 1. A method of delivering at least one therapeutic agent to a target , the method comprising:administering a particle to the target, wherein the particle comprises poly(lactide-co-glycolide)-graft-polyethylenimine (PLGA-g-PEI (PgP)) and the at least one therapeutic agent,wherein the particle is a micelle having an interior core and a shell having an exterior surface;wherein PLGA-g-PEI forms the micelle, and at least a portion of PLGA of PLGA-g-PEI forms at least a portion of the interior core and at least a portion of PEI of PLGA-g-PEI forms at least a portion of the exterior surface of the shell; andwherein the PLGA in the PLGA-g-PEI has a molecular weight in a range of about 20 kDaltons to about 70 kDaltons, thereby delivering the at least one therapeutic agent to the target.2. The method of claim 1 , wherein the interior core of the particle comprises the at least one therapeutic agent.3. The method of claim 1 , wherein the particle comprises at least two therapeutic agents.4. The method of claim 3 , wherein one of the at least two therapeutic agents is bound to a portion of the exterior surface of the shell and the other is present in the interior core of the particle5. The method of claim 3 , wherein the at least two therapeutic agents comprise an antiproliferative drug and antithrombotic drug.6. The method of claim 1 , wherein the particle further comprises at least one nucleic acid claim 1 , and the at least one therapeutic agent and the at least one nucleic acid are simultaneously delivered to the target.7. The method of claim 1 , wherein the particle further comprises at least one targeting moiety that is covalently conjugated to a portion of the ...

PRODRUG COMPOSITIONS, PRODRUG NANOPARTICLES, AND METHODS OF USE THEREOF

The present invention encompasses prodrug compositions, nanoparticles comprising one or more prodrugs, and methods of use thereof. 1. A composition for in vivo delivery of a compound to a target cell , the composition comprising a non-liposomal particle and at least one prodrug , wherein(a) the particle has an outer surface that is a membrane comprised of the at least one prodrug, and is further comprised of about 100% to about 60% phospholipid; and(b) the prodrug comprises a compound of less than about 3000 da linked to an acyl moiety of a phosphoglyceride, wherein the compound may be released from the phosphoglyceride backbone via enzyme cleavage, and(c) the particle is about 10 nm to about 20 nm in diameter.2. The composition of claim 1 , wherein the outer surface of the particle is comprised of not more than 3 mol % of a prodrug.3. The composition of claim 1 , wherein the outer surface of the particle is comprised of about 0.1 mol % of a prodrug to about 9% of a prodrug.4. The composition of claim 1 , wherein the non-liposomal particle is a micelle.5. The composition of claim 1 , wherein less than about 10% of the outer surface of the particle is cross-linked.6. The composition of claim 1 , wherein the outer surface further comprises a homing ligand.7. The composition of claim 6 , wherein the outer surface is not pegylated except for the homing ligand.8. The composition of claim 6 , wherein the homing ligand is selected from the group consisting of antibodies claim 6 , antibody fragments claim 6 , peptides claim 6 , asialoglycoproteins claim 6 , polysaccharides claim 6 , nucleic acids claim 6 , small molecules claim 6 , and peptidomimetics.9. The composition of claim 6 , wherein the homing ligand is selected from the group consisting of integrins αvβ3 claim 6 , α5β1 claim 6 , ICAM-1 claim 6 , VCAM-1 and VLA-4.10. The composition of claim 1 , wherein the compound is linked to the sn-2 acyl moiety of the phosphoglyceride.11. The composition of claim 10 , wherein ...

REAGENTS FOR INDUCING AN IMMUNE RESPONSE

The present disclosure relates to reagents (antigenic and/or immunogenic reagents) and kits that are useful in a variety of in vitro, in vivo, and ex vivo methods including, e.g., methods for inducing an immune response, or for generating an antibody, in a subject. The reagents described herein can be used in the treatment or prevention of HIV-1 infections. In addition, the disclosure provides methods and compositions useful for designing (or identifying) an agent that binds to an membrane proximal external region (MPER) of an HIV-1 gp160 polypeptide or an agent that inhibits the fusion of an HIV-1 particle to a cell. 1. A method for inducing an immune response in a subject , the method comprising administering to the subject a composition comprising:a particle encapsulated in lipid, wherein the particle comprises a solid material; anda protein consisting of:a membrane proximal external region (MPER) of an HIV-1 gp160 polypeptide; or a fragment of the HIV-1 gp160 polypeptide comprising the MPER,wherein the protein is no more than 100 amino acids in length and wherein at least one amino acid residue of the MPER that corresponds to position 669, 670, 672, 673, 675, or 678 of the HXB2 strain HIV-1 gp160 polypeptide is embedded in the lipid,wherein the reagent is capable of inducing HIV-1 broadly neutralizing antibodies in the subject.2. (canceled)3. The method of claim 1 , wherein the protein is no more than 60 amino acids in length.4. The method of claim 1 , wherein the protein is no more than 30 amino acids in length.5. The method of claim 1 , wherein the protein is no more than 22 amino acids in length.6. The method of claim 1 , wherein the MPER comprises the amino acid sequence X-L-X-X-W-X-X-X-W-X-W-X-X-I-X-X-W-L-W-Y-I-X(SEQ ID NO:1) claim 1 , wherein Xis A claim 1 , Q claim 1 , G claim 1 , or E; Xis D or S; Xis K claim 1 , S claim 1 , E claim 1 , or Q; Xis A claim 1 , S claim 1 , T claim 1 , D claim 1 , E claim 1 , K claim 1 , Q claim 1 , or N; Xis S claim 1 , G ...

TRIPLET-TRIPLET ENERGY TRANSFER WITH LIGHT EXCITATION AT LONG WAVELENGTHS AND METHODS THEREOF

The field of various phototriggered drug release and photoreactions, including reactions generally based on triplet-triplet energy transfer with light excitation at long wavelengths. Systems and methods for absorbing energy in a photosensitizer, and methods for making or using such systems, kits including such systems. The systems and methods comprise transferring that energy by triplet-triplet energy transfer to cleave a cleavable or other active moiety, for instance, in order to cause the release of a releasable moiety. In some cases, these may be contained within a suitable carrier material, for example, a particle or a micelle. Such systems and methods may be used in a variety of applications, including various biological or physical applications. For example, such systems and methods may be useful for delivering drugs or other releasable moieties to regions of a subject. 1. A composition , comprising: a photosensitizer; a cleavable moiety to accept triplet-triplet energy transfer from the photosensitizer in a higher energy state to cause cleavage of the cleavable moiety; and a releasable moiety releasable from the composition upon cleavage of the cleavable moiety , wherein the composition does not comprise an annihilator.2. The composition of wherein the photosensitizer comprises a transition metal-porphyrin.3. The composition of wherein the photosensitizer comprises a Pt porphyrin.4. The composition of wherein the photosensitizer is platinum (II) tetraphenyltetrabenzoporphyrin (PtTPBP).5. The composition of wherein the photosensitizer has an excitation wavelength of between about 600 nm claim 1 , and about 1200 nm.6. The composition of wherein the photosensitizer has an excitation wavelength of between 600 nm and about 700 nm.7. The composition of wherein the photosensitizer has an excitation wavelength of about 625 nm.8. The composition of wherein the cleavable moiety is photocleavable.9. The composition of wherein the cleavable moiety comprises a prodrug.10. ...

Polypeptide and Lipophilic Moiety Conjugate Compositions, Formulations, and Uses Related Thereto

In certain embodiments, this disclosure relates to pharmaceutical formulations for polypeptide and lipophilic moiety conjugates suitable for injection into humans and other animals and methods of preparation. In certain embodiments, the disclosure relates to a method of preparing the formulation comprising lyophilizing, solubilizing in ammonium acetate, filtering to create mono-disperse particles, re-lyophilizing, and solubilizing the micelles in a dextrose solution for injection.

Compositions for the delivery of rna and drugs into cells

Provided is a co-polymer of formula A-L-D, or a pharmaceutically acceptable salt thereof, wherein A is a linear, branched or dendritic polyamine; D is a lipid; and L is a linker comprising a water soluble polymer; wherein L is connected to A at a first end through a first covalent bond and connected to D at a second end through a second covalent bond.

Gemcitabine amphiphile prodrugs

The present invention relates to improved prodrugs, and compositions thereof. In particular, it relates to amphiphilic gemcitabine prodrugs or amphiphilic prodrugs of other biologically active molecules with the capacity to make liquid crystalline nanostructured nanoparticles, and uses thereof to treat animals, including humans.

IMMUNOSTIMULATORY NANOCARRIER

A formulation includes a carrier agent formed by conjugating an immunotherapy agent with a hydrophilic compound. The carrier agent further includes an interactive domain comprising at least one interactive moiety which interacts with a therapeutic agent. 1. A formulation , comprising:.a carrier agent formed by conjugating an immunotherapy agent with a hydrophilic compound, the carrier agent further comprising an interactive domain comprising at least one interactive moiety which interacts with a therapeutic agent.2. The formulation of wherein the immunotherapy agent is conjugated to the hydrophilic compound via a linkage which is labile in vivo.3. The formulation of wherein the at least one interactive moiety interacts with a chemotherapy agent.4. The formulation of wherein the immunotherapy agent affects programmed cell death protein claim 2 , indoleamine-pyrrole 2 claim 2 ,3-dioxygenase claim 2 , cytotoxic T-lymphocyte antigen 4(CTLA-4) claim 2 , PD-L1 claim 2 , PD-L2 claim 2 , lymphocyte activation gene 3(LAG3) claim 2 , or B7 homolog3(B7-H3)5. The formulation of wherein the interactive domain comprises at least one of a fluorenylmethyloxycarbonyl group claim 2 , a carbobenzyloxy group claim 2 , an isobutoxycarbamate group claim 2 , a naphthylacetyl group claim 2 , a carbazole group claim 2 , a quinolone group claim 2 , an isoquinolone group claim 2 , or a group which is a residue of a molecule selected from the group of the therapeutic agent claim 2 , a portion of the therapeutic agent claim 2 , (9H-fluoren-9-yl)methanamine claim 2 , (9H-fluoren-9-yl)methanol claim 2 , 9H-fluoren-9-amine claim 2 , naphthalene claim 2 , 1 claim 2 ,1′-bi-2-naphthol (BINOL) claim 2 , camptothecin claim 2 , a camptothecin analog claim 2 , pemetrexed claim 2 , docetaxel claim 2 , paclitaxel claim 2 , epirubicin claim 2 , doxorubicin claim 2 , vinblastine claim 2 , vindesine claim 2 , etoposide claim 2 , hydroxycamptothecin claim 2 , irinotecan claim 2 , mitoxantrone claim 2 , ...

Neurotherapeutic Nanoparticle Compositions and Devices

There are provided compositions and methods for treatment of neurodegeneative diseases and CNS injury. The compositions a pharmaceutically acceptable carrier solution; and a plurality of biodegradable nanoparticles, wherein the nanoparticles comprise a targeting moiety that is able to bind selectively to the surface of a neural stem cell and wherein the nanoparticles further comprise factors such as leukaemia inhibitory factor (LIF); XAV939 and/or one or more of : brain-derived neurotrophic factor (BDNF) or an agonist thereof; epidermal growth factor (EGF) or an agonist thereof; glial cell-derived neurotrophic factor (GDNF) or an agonist thereof; retinoic acid and derivatives thereof; ciliary neurotrophic factor (CTNF) or an agonist thereof; and Wnt5A. The biodegradable nanoparticles may deliver via controlled time release.

Nanoparticle emulsions

Composites formed from a liquid core encapsulated by a plurality of nanoparticles are provided herein. The composites in certain embodiments are droplets comprising a hydrophobic dispersed phase within a hydrophilic continuous phase, thereby forming an emulsion. The composites can be used as contrast agents for imaging, therapeutic agents, and adapted for other uses according to the unique properties of the composites disclosed herein.

POLYMERSOMES, LIPOSOMES, AND OTHER SPECIES ASSOCIATED WITH FLUIDIC DROPLETS

The present invention relates generally to vesicles such as liposomes, colloidosomes, and polymersomes, as well as techniques for making and using such vesicles. In some cases, the vesicles may be at least partially biocompatible and/or biodegradable. The vesicles may be formed, according to one aspect, by forming a multiple emulsion comprising a first droplet surrounded by a second droplet, which in turn is surrounded by a third fluid, where the second droplet comprises lipids and/or polymers, and removing fluid from the second droplet, e.g., through evaporation or diffusion, until a vesicle is formed. In certain aspects, the size of the vesicle may be controlled, e.g., through osmolarity, and in certain embodiments, the vesicle may be ruptured through a change in osmolarity. In some cases, the vesicle may contain other species, such as fluorescent molecules, microparticles, pharmaceutical agents, etc., which may be released upon rupture. Yet other aspects of the invention are generally directed to methods of making such vesicles, kits involving such vesicles, or the like. 127-. (canceled)28. A method of forming a polymersome comprising a species encapsulated therein , comprising:(a) generating a double emulsion comprising an outer phase substantially immiscible with a middle phase, which middle phase is in turn substantially immiscible with an inner phase, wherein said inner phase comprises a species, and wherein said middle phase comprises an amphiphilic diblock copolymer in a solvent, wherein the amphiphilic diblock copolymer comprising hydrophilic and hydrophobic blocks; and 'wherein a molecular weight ratio of said hydrophilic to hydrophobic blocks is selected such that said polymer membrane is degradable upon application of an osmotic pressure shock.', '(b) removing said solvent of said middle phase to form a polymer membrane, thereby yielding said polymersome comprising said species encapsulated therein,'}29. The method of claim 28 , wherein said outer phase ...

ANTIMICROBIAL PEPTIDE DERIVATIVE AND USE THEREOF

The invention relates to the field of biomedicine and particularly to a hydrophobically modified antimicrobial peptide and a use thereof. The technical problem to be solved by the invention is to provide a hydrophobically modified antimicrobial peptide, the hydrophobic modification is to couple a hydrophobic fragment at the nitrogen terminal of the antimicrobial peptide. The invention further provides a micelle prepared from the hydrophobically modified antimicrobial peptide, and use of the hydrophobically modified antimicrobial peptide and the micelle in preparing antimicrobial drugs, nucleic acid transporter, immune adjuvant and the like. Due to small molecular weight, the antimicrobial peptide of the invention can be conveniently synthesized by Fmoc solid phase polypeptide, and coupled to a hydrophobic fragment by the chemical synthesis method in a simple and feasible way. 1. A hydrophobically modified antimicrobial peptide , comprising an amino acid sequence VQWRIRVAVIRK (SEQ ID NO:1) with a hydrophobic fragment coupled to a nitrogen terminal of the amino acid sequence.2. The hydrophobically modified antimicrobial peptide according t claim 1 , wherein the antimicrobial peptide VQWRIRVAVIRK is modified by C-terminal amidation to produce VQWRIRVAVIRK-NH.3. The hydrophobically modified antimicrobial peptide according to claim 1 , wherein the hydrophobic fragment is a sterol compound or saturated straight-chain fatty acid.4. The hydrophobically modified antimicrobial peptide according t claim 3 , wherein the sterol compound is a cholesterol compound or a cholic acid compound.5. The hydrophobically modified antimicrobial peptide according to claim 3 , wherein the sterol compound is at least one of succinylated cholesterol claim 3 , cholic acid or deoxycholic acid.6. The hydrophobically modified antimicrobial peptide according to claim 3 , wherein the saturated straight-chain fatty acid is at least one of a C6 to C20 straight-chain fatty acid.7. The hydrophobically ...

POLYMERSOMES, COLLOIDOSOMES, LIPOSOMES, AND OTHER SPECIES ASSOCIATED WITH FLUIDIC DROPLETS

The present invention relates generally to vesicles such as liposomes, colloidosomes, and polymersomes, as well as techniques for making and using such vesicles. In some cases, the vesicles may be at least partially biocompatible and/or biodegradable. The vesicles may be formed, according to one aspect, by forming a multiple emulsion comprising a first droplet surrounded by a second droplet, which in turn is surrounded by a third fluid, where the second droplet comprises lipids and/or polymers, and removing fluid from the second droplet, e.g., through evaporation or diffusion, until a vesicle is formed. In certain aspects, the size of the vesicle may be controlled, e.g., through osmolarity, and in certain embodiments, the vesicle may be ruptured through a change in osmolarity. In some cases, the vesicle may contain other species, such as fluorescent molecules, microparticles, pharmaceutical agents, etc., which may be released upon rupture. Yet other aspects of the invention are generally directed to methods of making such vesicles, kits involving such vesicles, or the like. 127-. (canceled)28. A method of forming a polymersome comprising a species encapsulated therein , said method comprising:a. generating a double emulsion comprising an outer phase substantially immiscible with a middle phase, which middle phase is in turn substantially immiscible with an inner phase, wherein said inner phase comprises said species, and wherein said middle phase comprises an amphiphilic diblock copolymer in a solvent, wherein said amphiphilic diblock copolymer comprises hydrophilic and hydrophobic blocks; and wherein said removing comprises said solvent dewetting from said inner phase, wherein sad solvent comprises a mixture of a first fluid and a second fluid, wherein volume fractions of said first fluid and said second fluid in said mixture are selected such that said dewetting yields said polymerosome, and', 'wherein a molecular weight ratio of said hydrophilic to hydrophobic ...

TANDEM REPEAT CANCER-TARGETING PEPTIDES FOR MOLECULAR CONJUGATION OR ENGINEERING AND USES THEREOF IN CANCER THERANOSTICS

An isolated cancer-targeting peptide that includes at least two copies of the amino acid sequence PFLP (SEQ ID NO: 1) or PFLF (SEQ ID NO: 2). Also disclosed is a pharmaceutical composition for treating cancer. The composition contains the isolated cancer-targeting peptide and an anti-cancer agent. Further disclosed is a bispecific anti-cancer antibody that includes the isolated cancer-targeting peptide and an antigen-binding peptide that stimulates T cell activity. Methods are provided for treating cancer by administering the pharmaceutical composition or the bispecific anti-cancer antibody. Further provided is a method for diagnosing cancer by administering a radionuclide-labeled cancer-targeting peptide to an individual and imaging a location of the radionuclide. 1. An isolated cancer-targeting peptide , comprising at least two copies of the amino acid sequence PFLP (SEQ ID NO: 1) or PFLF (SEQ ID NO: 2).2. The isolated cancer-targeting peptide of claim 1 , wherein the peptide includes two overlapping copies of SEQ ID NO: 1.3. The isolated cancer-targeting peptide of claim 2 , having the amino acid sequence RPFLPFLPY (SEQ ID NO: 5) or RPFLPFLPYRPFLPFLPY (SEQ ID NO: 6).4. The isolated cancer-targeting peptide of claim 1 , wherein the peptide includes at least two copies of SEQ ID NO: 2.5. The isolated cancer-targeting peptide of claim 4 , having the amino acid sequence of RPFLFPFLFY (SEQ ID NO: 7) or RPFLFPFLFYRPFLFPFLFY (SEQ ID NO: 8).6. A pharmaceutical composition for treating cancer claim 1 , comprising the isolated cancer-targeting peptide of and an anti-cancer agent.7. The pharmaceutical composition of claim 6 , further comprising a micellar nanocomplex having a core encapsulating the anti-cancer agent and a shell that includes the isolated cancer-targeting peptide.8. The pharmaceutical composition of claim 7 , wherein the isolated cancer-targeting peptide is conjugated to polyethylene glycol.9. The pharmaceutical composition of claim 8 , wherein the anti- ...

RENAL CLEARABLE ORGANIC NANOCARRIERS

Disclosed herein are nanocarriers that include one or more cyclodextrin moieties conjugated to a polymer. The cyclodextrin moieties can complex therapeutic (e.g., anticancer) agents, and can be used to treat diseases such as cancer. 1. A nanocarrier , comprising one or more cyclodextrin moieties conjugated to a polymer.2. The nanocarrier of claim 1 , wherein the polymer defines a micelle claim 1 , a liposome claim 1 , a nanosphere claim 1 , a dendrimer claim 1 , or a hollow shell.3. The nanocarrier of claim 2 , wherein the polymer comprises ϵ-polylysine claim 2 , L-polylysine claim 2 , polylactic acid claim 2 , and poly(lactic-co-glycolic acid) claim 2 , polyaspartic acid claim 2 , polyglutamic acid claim 2 , or polyglutamic acid-poly(ethylene glycol) copolymer.4. The nanocarrier of claim 1 , wherein the cyclodextrin moiety is derived from α-cyclodextrin claim 1 , β-cyclodextrin claim 1 , γ-cyclodextrin claim 1 , 2-hydroxypropyl-β-cyclodextrin claim 1 , 2-hydroxypropyl-γ-cyclodextrin claim 1 , methyl-β-cyclodextrin claim 1 , a β-cyclodextrin thioether claim 1 , or a cyanoethylated β-cyclodextrin.5. The nanocarrier of claim 1 , wherein at least one cyclodextrin moiety is conjugated to an amino group of the polymer.6. (canceled)7. The nanocarrier of claim 1 , wherein the nanocarrier further comprises a contrast agent claim 1 , wherein the contrast agent is conjugated to the polymer.8. The nanocarrier of claim 7 , wherein the contrast agent comprises a near-infrared fluorophore selected from the group consisting of ZW800-1C claim 7 , ZW800-1 claim 7 , ZW800-3C claim 7 , ZW700-1 claim 7 , indocyanine green (ICG) claim 7 , Cys claim 7 , Cy5.5 claim 7 , Cy7 claim 7 , Cy7.5 claim 7 , IRDye800-CW (CW800) claim 7 , and ZWCC.9. (canceled)10. The nanocarrier of claim 1 , wherein the nanocarrier comprises one or more therapeutic agents that form a complex with the one or more cyclodextrin moieties.11. The nanocarrier of claim 10 , wherein the one or more therapeutic agents ...

CONJUGATED LIPOMERS AND USES THEREOF

The present invention provides inventive conjugated polyethyleneimine (PEI) polymers and conjugated aza-macrocycles (collectively referred to herein as “conjugated lipomers” or “lipomers”) containing one or more groups of the formula (iii): 24-. (canceled)5. The conjugated lipomer of claim 1 , wherein the conjugated lipomer is prepared from a polyethyleneimine polymer having a number average molecule weight (Mn) of less than 800 g/mol.6. The conjugated lipomer of claim 1 , wherein each instance of Ris independently hydrogen or a group of the formula (iii′).7. The conjugated lipomer of claim 1 , wherein Z is hydrogen or a group of the formula (iii′).8. The conjugated lipomer of claim 1 , wherein n is an integer of 3 to 5 claim 1 , inclusive.9. The conjugated lipomer of claim 1 , wherein each instance of Ris independently hydrogen; a substituted or unsubstituted polyethyleneimine; or a group of the formula (iii′).10. The conjugated lipomer of claim 1 , wherein at least one Lgroup is of the formula (ii).1112-. (canceled)13. The conjugated lipomer of claim 1 , wherein each instance of Ris substituted or unsubstituted alkyl.1437-. (canceled)38. A composition comprising one or more conjugated lipomers of claim 1 , and claim 1 , optionally claim 1 , an excipient.39. The composition of claim 38 , wherein the composition is a pharmaceutical composition or a cosmetic composition.40. The composition of claim 38 , wherein the composition further comprises an agent.41. The composition of claim 40 , wherein the agent is an organic molecule claim 40 , inorganic molecule claim 40 , nucleic acid claim 40 , protein claim 40 , peptide claim 40 , polynucleotide claim 40 , targeting agent claim 40 , an isotopically labeled chemical compound claim 40 , vaccine claim 40 , or an immunological agent.42. The composition of claim 41 , wherein the agent is a polynucleotide claim 41 , and the polynucleotide is DNA or RNA.43. The composition of claim 42 , wherein the RNA is RNAi claim 42 , dsRNA ...

POLYION COMPLEX CAPABLE OF EFFICIENTLY DELIVERING MRNA INTO LIVING BODY, AND DRUG AND METHOD FOR TREATING ARTHROPATHY IN WHICH SAID COMPLEX IS USED

The present invention provides a polyion complex which can efficiently deliver mRNA into a living body as well as a therapeutic agent and a therapeutic method of arthropathy in which the polyion complex is used. For example, there is provided a polyion complex comprising a cationic polymer and mRNA, wherein the cationic polymer is a polymer comprising a cationic unnatural amino acid as a monomer unit and the cationic unnatural amino acid is an amino acid having a group represented by —(NH—(CH))—NH, wherein p is 2, 3 or 4, as a side chain. 1. A polyion complex comprising a cationic polymer and mRNA ,{'sub': 2', '2', 'p', '2, 'wherein the cationic polymer is a polymer comprising a cationic unnatural amino acid as a monomer unit and the cationic unnatural amino acid is an amino acid having a group represented by —(NH—(CH))—NH, wherein p is 2, 3 or 4, as a side chain.'}2. The polyion complex according to claim 1 , wherein the cationic polymer is a block copolymer with polyethylene glycol.4. A pharmaceutical composition for treating arthropathy claim 1 , comprising the polyion complex according to any one of to claim 1 ,wherein the mRNA is an mRNA of a factor promoting joint formation.5. The pharmaceutical composition according to claim 4 , wherein p is 3 or 4.6. The pharmaceutical composition according to claim 5 , wherein p is 4.7. The pharmaceutical composition according to any one of to claim 5 , wherein the pharmaceutical composition is administered once every 2 days or once every 3 days.8. The pharmaceutical composition according to or claim 5 , wherein the pharmaceutical composition is administered once every 7 days.9. The pharmaceutical composition according to any one of to claim 5 , wherein the arthropathy is osteoarthritis or rheumatoid arthritis.10. A delivery agent for use in delivering mRNA into cells claim 3 , comprising the polyion complex according to claim 3 , wherein p is 3 or 4.11. The delivery agent according to claim 10 , wherein p is 4. This ...

THERMORESPONSIVE BIOCONJUGATES AND THEIR CONTROLLED DELIVERY OF CARGO

The present invention provides a bioconjugate. The bioconjugate comprises a first molecule comprising an elast-in-like peptide (ELP), a second molecule capable of self-associating into an oligomer, and a linker connecting the first molecule with the second molecule. The bioconjugate is self-assembled into particles, which are disassembled when the temperature is increased. Also provided is a method for delivering a bioconjugate to a target matrix, comprising (a) introducing a bioconjugate self-assembled into particles to a target matrix, wherein the bioconjugate comprises a first molecule comprising an elastin-like peptide (ELP), a second molecule capable of self-associating into an oligomer, and a linker connecting the first molecule with the second molecule, and (b) increasing the temperature of the target matrix to disassemble the particles at the target matrix. 1. A method for delivering a bioconjugate to a target matrix , comprising(a) introducing a bioconjugate self-assembled into particles to a target matrix, wherein the bioconjugate comprises a first molecule comprising an elastin-like peptide (ELP), a second molecule capable of self-associating into an oligomer, and a linker connecting the first molecule with the second molecule, and(b) increasing the temperature of the target matrix to disassemble the particles at the target matrix.2. (canceled)3. (canceled)4. The method of claim 1 , wherein the ELP comprises 3-25 repeats of VPGXG (SEQ ID NO: 22) claim 1 , XPGVG (SEQ ID NO: 28) or XPAVG (SEQ ID NO: 27) claim 1 , wherein X is an amino acid.5. The method of claim 1 , wherein the ELP is VPGXGVPGXGVPGXG (SEQ ID NO: 23) claim 1 , VPGXGVPGXGVPGXGVPGXG (SEQ ID NO: 24) claim 1 , VPGXGVPGXGVPGXGVPGXGVPGXG (SEQ ID NO: 25) or VPGXGVPGXGVPGXGVPGXGVPGXGVPGXG (SEQ ID NO: 26) claim 1 , wherein X is an amino acid.6. The method of claim 1 , wherein the ELP is VPGFGVPGFGVPGFGVPGFGVPGFGVPGFG (SEQ ID NO: 21).7. The method of claim 1 , wherein the second molecule comprises a ...

POLY(CYCLIC IMINO ETHER)S

The invention relates to invention relates to a statistical copolymer represented by the following formula (I): Ini-[Ox]-[Oz]-Nuc (I) wherein: Ini represents a residue of an initiator of cationic polymerization, Nuc represents a residue of a nucleophilic agent, Ox represents N(R)CHRCHR; each Rindependently represents H or C(O)R; and Rindependently represents optionally substituted Calkyl, optionally substituted cycloalkyl, optionally substituted aralkyl or optionally substituted aryl; Oz represents N(R)CHRCHRCHR; each Rindependently represents C(O)Ror H; and Rindependently represents optionally substituted Calkyl, optionally substituted cycloalkyl, optionally substituted aralkyl or optionally substituted aryl; each Rindependently represents H, linear or branched Calkyl; m≥5; n≥5; m+n≥20; 3:97≤m:n≤97:3. The statistical copolymers of the present invention exhibit useful properties that can be exploited in the medical field, especially in polymer micelles for drug delivery and polyplexes for DNA delivery. 115-. (canceled)16. A statistical copolymer represented by the following formula (I):{'br': None, 'sub': m', 'n, 'Ini-[Ox]-[Oz]-Nuc \u2003\u2003(I)'} (a) Ini represents a residue of an initiator of cationic polymerization,', '(b) Nuc represents a residue of a nucleophilic agent,', {'sup': 1', 'a', 'a', '1', '11, '(c) Ox represents N(R)CHRCHR; each Rindependently represents H or C(O)R; and'}, {'sup': '11', 'sub': '1-12', 'Rindependently represents optionally substituted Calkyl, optionally substituted cycloalkyl, optionally substituted aralkyl or optionally substituted aryl;'}, {'sup': 2', 'a', 'a', 'a', '2', '21', '21, 'sub': '1-12', '(d) Oz represents N(R)CHRCHRCHR; each Rindependently represents C(O)Ror H; and Rindependently represents optionally substituted Calkyl, optionally substituted cycloalkyl, optionally substituted aralkyl or optionally substituted aryl;'}, {'sup': 'a', 'sub': '1-3', '(e) each Rindependently represents H, linear or branched Calkyl;'}, '(f) m≥ ...

Use of the tas1r3 protein as a marker for therapeutic, diagnostic, and/or prognostic purposes for tumors that express said protein

In the present invention, the use of the TAS1R3 receptor as a biomarker for application in cancer diagnosis, monitoring, and therapy is described for the first time. In this sense, the authors of the present invention have demonstrated that TAS1R3 is a biomarker of interest in oncology, useful for the diagnosis of the disease, and capable of providing relevant information thereupon, to monitor the evolution, select the treatment, and selectively direct therapeutic molecules. It has been determined that it is possible to identify therapies against this receptor, and that it is also possible to direct conjugates and controlled release systems of drugs, such as nanoparticles, observing a very effective intracellular accumulation thereof in primary, disseminated and metastatic tumor cells. On the other hand, the presence of TAS1R3 in circulating tumor cells (CTCs) has also been demonstrated. These are tumor cells released into the bloodstream by the primary tumor and are considered key factors in the creation of metastases, so that their detection in early stages will serve as an early detector of metastasis, and are also useful in monitoring the disease and evaluating of the response to drugs.

NANOSYSTEMS AS SELECTIVE VEHICLES

In the present invention, the development of various oil-in-water (O/W) nanoemulsions containing an oil phase or oil core, preferably selected from vitamin E or oleic acid, stabilized by a sphingolipid of the sphingomyelin type, and optionally other lipids such as phospholipids, cholesterol, octadecylamine, DOTAP (N-[1-(2,3-Dioleoyloxy) propyl]-N, N, N-trimethylammonium methyl-sulfate), and PEGylated derivatives (derivatives with polyethylene glycol), for use as a nanotech vehicle, in particular for the management of cancer and metastatic disease, is herein described. Said nanoemulsions can be functionalized with ligands capable of interacting or binding to receptors expressed on the cell membrane of tumor cells, and in particular capable of interacting or binding to receptors expressed on the membrane of primary and/or disseminated or metastatic tumor cells. Also, antitumor drugs or therapeutic biomolecules can be encapsulated in said nanoemulsions and, finally, contrast agents can be incorporated for their use in the in vivo diagnosis in said nanoemulsions. 1. Oil in water (o/w) nanoemulsion , comprising:a. An aqueous phase;b. An oily nucleus comprising α-tocopherol (vitamin E); andc. Sphingomyelin.2. The nanoemulsion claim 1 , according to claim 1 , wherein said nanoemulsion is functionalized with at least one of the following elementsa. Therapeutic molecules; andb. Contrast agents.3. The nanoemulsion claim 2 , according to claim 2 , wherein said therapeutic molecules are selected from the list consisting of: antitumor drugs such as carmofur claim 2 , etoposide docetaxel claim 2 , 5-Fluoracil claim 2 , paclitaxel claim 2 , gemcitabine claim 2 , and edelfosine claim 2 , or derivatives thereof; anti-inflammatory or anti-angiogenic drugs claim 2 , such as curcumin claim 2 , verteporfin claim 2 , and resveratrol; nucleic acids such as pDNAs claim 2 , shRNAs claim 2 , miRNAs or mRNAs; biomolecules such as peptides claim 2 , antibodies or fragments thereof claim 2 , ...

Methylene blue complex for treating skin disease and its use thereof

The present invention relates to complex particles using methylene blue for treating a skin disease caused by or and a composition for treatment including the complex particles. The complex particles in the present invention can be used as a photosensitizer for a photodynamic therapy and complex particles having a micelle form in which hydrophilic methylene blue and two hydrophobic organic acids are combined, and as a result, pore penetration is easy and an occlusion time can be significantly reduced to 30 minutes as compared with conventional phototherapy requiring an occlusion time of 1 hour to 3 hours. Further, in order to reduce side effects of a residual photosensitizer in phototherapy using an existing photosensitizer due to photoreaction and photobleaching of the methylene blue-organic acid complex, a light protection (light blocking or light shielding) time when contact of light needs to be avoided for 24 hours or more after treatment can be significantly reduced to 3 hours, and target treatment for , or the like which is a cause of acne is possible. 1. A methylene blue complex for phototherapy of a skin disease , comprising a methylene blue and two kinds of organic acids , wherein the complex has a micelle form in which the methylene blue is positioned at the center of the complex and the organic acids are positioned on the outside of the methylene blue.2. The methylene blue complex for phototherapy of a skin disease of claim 1 , wherein the organic acids are two kinds of organic acids selected from docosahexaenoic acid (DHA) claim 1 , indole-3-acetic acid (IAA) claim 1 , tranexamic acid claim 1 , salicylic acid claim 1 , ascorbic acid claim 1 , linoleic acid claim 1 , linolenic acid claim 1 , oleic acid claim 1 , deoxycholic acid claim 1 , folic acid claim 1 , retinoic acid claim 1 , cholic acid claim 1 , glycocholic acid claim 1 , taurocholic acid claim 1 , chenodeoxycholic acid claim 1 , glycochenodeoxycholic acid claim 1 , taurochenodeoxycholic acid ...

Pharmaceutical composition containing anionic drug, and preparation method therefor

Disclosed are a pharmaceutical composition for anionic drug delivery, and a preparation method therefor, the pharmaceutical composition for anionic drug delivery containing: an anionic drug as an active ingredient; a cationic compound; an amphiphilic block copolymer; and a polylactate, wherein the anionic drug formed a complex with the cationic lipid, and the complex is encapsulated within a micelle structure formed by the amphiphilic block copolymer and the polylactate.

Block copolymers for stable micelles

The present invention relates to the field of polymer chemistry and more particularly to multiblock copolymers and micelles comprising the same. Compositions herein are useful for drug-delivery applications.

UNDECYLENIC ACID-BASED NANOCARRIERS FOR TARGETED DRUG DELIVERY

Targeted drug delivery systems comprising a therapeutic agent solubilized with undecylenic acid (UA)-based nanocarrier vesicles that may be polymerized or provided as an mPEG ester are provided to achieve targeted delivery of, for example, ROS-activated cytotoxic agents to cancer cells exhibiting high levels of ROS. Methods utilizing photodynamic and sonodynamic generation of ROS to enhance targeted delivery are also provided. 1. A targeted drug delivery system comprising a chemotherapeutic agent solubilized with undecylenic acid (UA)-based nanocarrier vesicles selected from monomeric UA-based nanocarrier vesicles , polymeric UA-based nanocarrier vesicles , monomeric UA-based nanocarrier vesicles bonded to methoxy polyethylene glycol (mPEG) , and polymeric UA-based nanocarrier vesicles bonded to mPEG.2. The targeted drug delivery system according to claim 1 , wherein an average hydrodynamic diameter of the nanocarrier vesicles is between about 5 nm and about 200 nm.3. The targeted drug delivery system according to comprising PEGylated UA-based nanocarrier vesicles having an average hydrodynamic diameter of about 65 nm.4. The targeted drug delivery system according to claim 1 , wherein the chemotherapeutic agent comprises at least one reactive oxygen species (ROS)-activated cytotoxic agent (RAC).5. The targeted drug delivery system according to claim 4 , wherein at least one RAC comprises a molecule selected from Table 5.6. The targeted drug delivery system according to claim 5 , wherein the at least one RAC comprises RAC1 and/or a derivative of RAC1.6. The targeted drug delivery system according to claim 5 , comprising at least one agent selected from Table 6.8. A pharmaceutical composition comprising a drug delivery system according to .9. A method of treating a subject suffering from a proliferative disorder associated with an increased presence of ROS claim 1 , the method comprising administering a pharmaceutical composition comprising a targeted drug delivery ...

NANOPARTICULATE DRUG DELIVERY SYSTEMS

Described herein are compositions that include an assembly of self-assembling conjugates. The self-assembling conjugates may include a polypeptide having a transition temperature (17) above 50° C. when the polypeptide is not attached to the conjugate, an albumin binding domain (ABD) attached to a first end of the polypeptide, and at least one molecule attached to a second end of the polypeptide through a cysteine group, wherein the molecule has an octanol-water distribution coefficient (log D) of greater than or equal to 1.5 at a pH of 7.4 when the molecule is not attached to the conjugate. Also described herein are methods of using the compositions. 1. A composition comprising: [{'sub': 't', 'a polypeptide having a transition temperature (T) above 50° C. when the polypeptide is not attached to the conjugate;'}, 'an albumin binding domain (ABD) attached to a first end of the polypeptide; and', 'at least one molecule attached to a second end of the polypeptide through a cysteine group, wherein the molecule has an octanol-water distribution coefficient (log D) of greater than or equal to 1.5 at a pH of 7.4 when the molecule is not attached to the conjugate,, 'an assembly of self-assembling conjugates, each self-assembling conjugate comprising'}{'sub': 't', 'wherein the conjugate has a Tabove 40° C. at a concentration of 100 μM.'}2. A composition comprising: [{'sub': 't', 'a polypeptide having a transition temperature (T) above 50° C. when the polypeptide is not attached to the conjugate;'}, {'sub': t', 't, "an albumin binding domain (ABD) attached to a first end of the polypeptide, wherein the ABD attached to the polypeptide lowers the Tof the polypeptide no more than 5° C. relative to the polypeptide's Twhen the polypeptide is not attached to the ABD or the conjugate; and"}, 'at least one molecule attached to a second end of the polypeptide through a cysteine group, wherein the molecule has an octanol-water distribution coefficient (log D) of greater than or equal to ...

POLY(HISTIDINE)-BASED MICELLES FOR COMPLEXATION AND DELIVERY OF PROTEINS AND NUCLEIC ACIDS

Disclosed are compositions for delivering gene editing molecules to a cell. Exemplary compositions comprise a micelle assembled from a plurality of triblock copolymers, wherein each triblock copolymer having at least one hydrophobic block, at least one hydrophilic block, and at least one poly(L-histidine) block, wherein: the at least one poly(L-histidine) block complexes with the at least one gene editing molecule; and the at least one poly(L-histidine) block is capable of a pH dependent release of the at least one gene editing molecule. 1. A composition for delivering at least one gene editing molecule to a cell , the composition comprising:a micelle assembled from a plurality of triblock copolymers, wherein each triblock copolymer having at least one hydrophobic block, at least one hydrophilic block, and at least one poly(L-histidine) block, the at least one poly(L-histidine) block complexes with the at least one gene editing molecule; and', 'the at least one poly(L-histidine) block is capable of a pH dependent release of the at least one gene editing molecule., 'wherein2. The composition of claim 1 , wherein the at least one gene editing molecule comprises one or more of a protein or a nucleic acid encoding for a protein claim 1 , wherein the protein is selected from the group comprising a transposase claim 1 , a nuclease claim 1 , and an integrase.3. The composition of claim 2 , wherein the nuclease is selected from the group comprising:a CRISPR associated protein 9 (Cas9);a type IIS restriction enzyme;a transcription activator-like effector nuclease (TALEN); anda zinc finger nuclease (ZFN).4. The composition of claim 1 , wherein the at least one gene editing molecule comprises one or more transposable element.5. The composition of claim 4 , wherein the one or more transposable element comprises a piggyBac transposon claim 4 , a Sleeping Beauty transposon or a LINE-1 (L1) transposon.6. The composition of claim 4 , wherein the at least one gene editing molecule ...

SMALL POLYMERIC CARRIERS FOR DELIVERY OF AGENTS

A polymer includes a hydrophobic polymer backbone, a first plurality of pendant groups attached to the hydrophobic polymer backbone and including at least one group including a plurality of hydroxyl groups, and a second plurality of pendant groups attached to the hydrophobic polymer backbone and comprising at least one hydrophilic polymer. 1. A polymer , comprising: a hydrophobic polymer backbone , a first plurality of pendant groups attached to the hydrophobic polymer backbone and comprising at least one group comprising a plurality of hydroxyl groups , and a second plurality of pendant groups attached to the hydrophobic polymer backbone and comprising at least one hydrophilic polymer , wherein at least one of the first plurality of pendant groups or the second plurality of pendant groups is attached to the hydrophobic polymer backbone via a linking moiety comprising at least one group which is interactive via π-π stacking.2. (canceled)3. (canceled)4. The polymer of wherein the first plurality of pendant groups is attached to the hydrophobic polymeric backbone via a first linking group comprising at least a first group which is interactive via π-π stacking.5. The polymer of wherein the at least a first group interactive via π-π stacking comprises an aromatic group.6. The polymer of wherein the at least a first group interactive via π-π stacking comprises a benzyl group.7. (canceled)8. (canceled)9. (canceled)10. The polymer of wherein the at least one group comprising a plurality of hydroxyl groups is a hydrophilic group.11. (canceled)12. (canceled)13. (canceled)14. (canceled)15. (canceled)16. (canceled)17. (canceled)18. (canceled)19. The polymer of wherein the nucleoside is selected from the group consisting of a gemcitabine claim 20 , azacytidine claim 20 , cytarabine claim 20 , or a biologically active derivative thereof.20. The polymer of wherein the therapeutic agent is a nucleoside.21. The polymer of wherein the at least one group comprising a plurality of ...

SURFACTANTS AND METHODS FOR MAKING SAME

Disclosed herein are surfactants consisting of a hydrophilic segment having repeating units and a first end and a second end. In these surfactants, the first end has a hydrophilic first end group and the second end has a hydrophobic second end group. These surfactants form micelles. Also disclosed herein are methods for making these surfactants and for using them in formulations with biologically active materials. 1. A surfactant consisting of a hydrophilic segment having repeating units and a first end and a second end;the first end having a hydrophilic first end group; and the first end group comprises from 2 to 20 carbons;', 'the second end group comprises a linker and a hydrophobic unit, wherein the hydrophobic unit comprises from 6 to 40 carbons; and', 'the ratio of the molar mass of the hydrophilic segment in kg/mol to the number of carbons in the second end group is from about 0.05 to about 1., 'the second end having a second end group; wherein'}2. The surfactant of claim 1 , wherein the linker is a chain transfer agent (CTA) group or a reversible addition-fragmentation chain-transfer polymerization (RAFT) group.3. (canceled)4. The surfactant according to claim 1 , wherein the ratio of the molar mass of the hydrophilic segment in kg/mol to the number of carbons in the second end group is from about 0.05 to 0.36.5. The surfactant according to claim 1 , wherein the molar mass of the hydrophilic segment is less than about 20 kg/mol.6. The surfactant according to claim 1 , wherein the repeating units are the same.7. The surfactant of claim 6 , wherein the unit of the hydrophilic segment is derived from an N-isopropylacrylamide monomer claim 6 , an N claim 6 ,N-dimethylacrylamide monomer claim 6 , or an N-hydroxyethylacrylamide monomer.8. The surfactant according to claim 1 , wherein the hydrophobic unit of the second end group is alkyl.9. The surfactant according to claim 1 , wherein the first end group comprises an alcohol or carboxylic acid.11. A mixture of the ...

Neurotherapeutic Nanoparticle Compositions Comprising Leukemia Inhibitory Factor

There are provided compositions and methods for treatment of neurodegeneative diseases and CNS injury. The compositions a pharmaceutically acceptable carrier solution; and a plurality of biodegradable nanoparticles, wherein the nanoparticles comprise a targeting moiety that is able to bind selectively to the surface of a neural stem cell and wherein the nanoparticles further comprise factors such as leukaemia inhibitory factor (LIF); XAV939 and/or one or more of: brain-derived neurotrophic factor (BDNF) or an agonist thereof; epidermal growth factor (EGF) or an agonist thereof; glial cell-derived neurotrophic factor (GDNF) or an agonist thereof; retinoic acid and derivatives thereof; ciliary neurotrophic factor (CTNF) or an agonist thereof; and Wnt5A. The biodegradable nanoparticles may deliver via controlled time release.

Treatment of age-related macular degeneration

A means of treating both the “dry” and/or “wet” forms of Age-Related Macular Degeneration (ARMD) using a disease targeting drug delivery system in which an anti-inflammatory drug is incorporated into nanoparticles such as liposomes, micelles, dendrimers, lipid nanospheres, nanoemulsions and the like. The nanoparticles are coated with an anti-Vascular Endothelial Growth Factor Receptor (VEGFR) targeting agent such as anti-VEGFR antibodies, anti-VEGFR aptamers, anti-VEGFR binding peptides and the like. Upon administration into the eye of a patient with ARMD the targeting agent on the nanoparticle will bind to VEGFR on neovascular cells in the retina and inhibit the abnormal proliferation of new blood vessels. In addition to its therapeutic action the targeting agent by binding to its receptor will anchor the drug delivery vehicle at the site of inflammation where the anti-inflammatory drug is released for maximum effect in inhibiting the local inflammatory response.

Siderophore-polymer conjugates for increasing bacterial sensitivity to antibiotics

The present technology provides siderophore-polymer conjugates that enhance the sensitivity of bacteria to antibiotics, e.g., Pseudomonas, P. aeruginosa, Acinetobacter, and A. baumannii. Methods of preparing and using such conjugates to treat bacterial infections are disclosed.

NANOCARRIER FOR SELECTIVE FLUORESCENCE LABELING OF CANCER CELL AND PREPARATION METHOD THEREFOR

An embodiment of the present invention provides a nanocarrier in a micelle structure, a pharmaceutical composition for diagnosis of cancer, comprising the same nanocarrier, and a method for preparing the same nanocarrier. The nanocarrier is obtained by dispersing a water-in-oil nanoemulsion containing an oil phase ingredient, a surfactant, and an aqueous phase ingredient inclusive of a cancer cell fluorescence-inducing substance and a cancer cell-targeting polysaccharide in water to remove the oil phase ingredient, whereby the nanocarrier includes the aqueous phase ingredient. 1. A micelle structured nanocarrier comprising an aqueous phase ingredient , the aqueous phase ingredient obtained by dispersing , in water , a water-in-oil nanoemulsion comprising an oil phase ingredient , a surfactant , and the aqueous phase ingredient to remove the oil phase ingredient , wherein the aqueous phase ingredient comprises a fluorescence-inducing substance and a cancer cell-targeting polysaccharide.2. The nanocarrier of claim 1 , wherein the micelle structured nanocarrier has an interpenetrating polymer network structure.3. The nanocarrier of claim 1 , wherein the micelle structured nanocarrier has an average particle size of 200 nm or less.4. The nanocarrier of claim 1 , wherein the nanocarrier has an average particle size of 200 nm or less and a zeta potential value of −10 mV to −30 mV or 10 mV to 30 mV.5. The nanocarrier of claim 1 , wherein the nanoemulsion comprises 70% by weight to 80% by weight of the oil phase ingredient claim 1 , 10% by weight to 20% by weight of the aqueous phase ingredient claim 1 , and 5% by weight to 15% by weight of the surfactant claim 1 , based on the total weight of the nanoemulsion.6. The nanocarrier of claim 1 , wherein the surfactant is a single surfactant or a cosurfactant.7. The nanocarrier of claim 1 , wherein the surfactant is a cosurfactant having an HLB value of 6 to 9.8. The nanocarrier of claim 1 , wherein the surfactant is a mixture ...

MICELLE COMPOSITION FOR NUCLEIC ACID DELIVERY USING TEMPERATURE-SENSITIVE POLYMER AND METHOD FOR PRODUCING SAME

Provided are a micelle composition for nucleic acid delivery using a temperature-sensitive polymer, and a method for producing the micelle. For example, provided is a polyion complex comprising a temperature-sensitive copolymer and a nucleic acid, wherein the temperature-sensitive copolymer comprises a cationic block and a temperature-sensitive block, the cationic block optionally carrying a hydrophilic block linked thereto, and the polyion complex is obtained by mixing the temperature-sensitive copolymer with the nucleic acid under temperature conditions equal to or lower than the lower critical solution temperature (LCST) of the temperature-sensitive copolymer. 1. A polyion complex comprising a temperature-sensitive copolymer and a nucleic acid , whereinthe temperature-sensitive copolymer comprises a cationic block and a temperature-sensitive block, andthe polyion complex is obtained by mixing the temperature-sensitive copolymer with the nucleic acid under temperature conditions equal to or lower than the lower critical solution temperature (LOST) of the temperature-sensitive copolymer.2. The polyion complex according to claim 1 , wherein the cationic block is a cationic amino acid polymer block.3. The polyion complex according to claim 1 , wherein the temperature-sensitive copolymer comprises a hydrophilic block claim 1 , and the hydrophilic block is polyethylene glycol.4. The polyion complex according to claim 1 , wherein the temperature-sensitive copolymer is modified with a GLUT1 ligand.5. The polyion complex according to claim 1 , wherein the nucleic acid is modified with a biocompatible hydrophobic group.6. The polyion complex according to claim 1 , wherein the nucleic acid is an siRNA.7. A composition for preparing a polyion complex comprising a temperature-sensitive copolymer claim 1 , wherein the temperature-sensitive copolymer comprises a cationic block and a temperature-sensitive block.8. The composition according to claim 7 , wherein the cationic block ...

BRANCHED PEPTIDES FOR ENZYMATIC ASSEMBLY AND MITOCHONDRIA DRUG DELIVERY

The present invention relates to a branched peptide that includes a first peptide chain and a second peptide chain having its C-terminal amino acid covalently linked to a sidechain of an amino acid residue of the first peptide chain, wherein the first peptide chain includes a plurality of aromatic amino acids and, optionally, an aromatic group linked to an amino terminus of the first peptide chain; and the second peptide chain includes a plurality of hydrophilic amino acids and an enzyme cleavage site. Pharmaceutical compositions containing the branched peptide and one or more therapeutic agents in an aqueous medium are disclosed, where the branched peptides form micelle structures in the aqueous medium. Methods of using the pharmaceutical composition to deliver therapeutic agents, and for treating various disease conditions are also described. 1. A branched peptide comprising:a first peptide chain and a second peptide chain having its C-terminal amino acid covalently linked to a sidechain of an amino acid residue of the first peptide chain, whereinthe first peptide chain comprises a plurality of aromatic amino acids and, optionally, an aromatic group linked to an amino terminus of the first peptide chain; andthe second peptide chain comprises a plurality of hydrophilic amino acids and an enzyme cleavage site.2. The branched peptide according to claim 1 , wherein the first peptide chain comprises the aromatic group linked to the amino terminus of the first peptide chain.3. The branched peptide according to claim 1 , wherein the aromatic group is selected from the group consisting of phenylacetyl claim 1 , naphthylacetyl claim 1 , fluorenylacetyl claim 1 , pyrenylacetyl claim 1 , and cinnamoyl.4. The branched peptide according to claim 1 , wherein the plurality of aromatic amino acids are selected from the group consisting of phenylalanine claim 1 , tyrosine claim 1 , and tryptophan.5. The branched peptide according to claim 1 , wherein the amino acid residue having ...

MAGNETIC PARTICLE CONJUGATES, MICELLES, AND METHODS OF DELIVERING AGENTS

Embodiments of the present disclosure provide for magnetic particle conjugates, methods of making the magnetic particle conjugates, methods of using magnetic particle conjugates, micelles (also referred to as a “magnetic composite nanocarrier” (MC-NC)), methods of making micelles, methods of using micelles, and the like. 2. The composition of claim 1 , wherein Q is selected from a retro-Diels-Alder-agent group or an azo group.4. The composition of claim 1 , wherein the magnetic particle is a material represented by MMFeO claim 1 , where each of Mand Mare independently selected from Fe claim 1 , Co claim 1 , Mn claim 1 , Zn claim 1 , Ta claim 1 , Sr claim 1 , or Ni claim 1 , wherein x is 0 to 1 claim 1 , wherein Mand Mare different metals.5. The composition of claim 4 , wherein the magnetic particle is a material selected from the group consisting of: FeO claim 4 , γFeO claim 4 , αFeO claim 4 , MnFeO claim 4 , ZnFeO claim 4 , or MnZnFeO.7. The composition of claim 6 , wherein w is 14 claim 6 , x is 11 claim 6 , y is 40 and z is 10.8. The composition of claim 1 , wherein the agent includes a drug claim 1 , a therapeutic agent claim 1 , a radiological agent claim 1 , or a biological agent.9. The composition of claim 1 , wherein the polymer fully encapsulates both the agent and the magnetic particles.10. (canceled)11. A composition claim 1 , comprising:a micelle including a plurality of magnetic particles, a plurality of amphiphilic polymers, and a plurality of agents, wherein the amphiphilic polymer has a hydrophobic region and a hydrophilic region, wherein the hydrophobic region of the amphiphilic polymer is located in a central region of the micelle and the hydrophilic region is located away from the central region and forms the micelle outer boundary, wherein a portion of magnetic particles and a portion of the agents are located in the central region of the micelle, and wherein the amphiphilic polymer contains thermally labile backbone bonds.12. The composition of ...

Delivery method of target material into extracellular vesicles using extracorporeal shockwave

Provided are a method of delivering target materials into extracellular vesicles including exposing the target materials and the extracellular vesicles to extracorporeal shockwaves, a method of preparing target material-introduced extracellular vesicles, extracellular vesicles prepared by the method, drug delivery vehicles including extracellular vesicles, and a method of delivering target materials into cells. The present disclosure exposes extracellular vesicles derived from natural organisms such as animal cells, plant cells, and microorganisms including bacteria and eukaryotic bacteria as well as artificially produced extracellular vesicles to extracorporeal shockwaves extracellularly. Thus, the high-level energy extracorporeal shockwaves can be used to deliver the target material into the extracellular vesicle efficiently. When treating with extracorporeal shockwaves, the ability of target material-introduced extracellular vesicles to incorporate into target cells also increases. According to the method of the present disclosure, the target materials can be delivered into cells with high efficiency, being utilized in various fields.

TRIPLET-TRIPLET ANNIHILATION-BASED UPCONVERSION

The present invention generally relates to various photoreactions, including reactions generally based on triplet-triplet annihilation upconversion. One aspect of the present invention is directed to systems and methods for absorbing energy (e.g., from a photon) in a photo sensitizer, transferring that energy by triplet-triplet energy transfer to an annihilator to produce a higher energy state via upconversion, then transferring that energy to cleave a cleavable or other active moiety, for instance, in order to cause the release of a releasable moiety. The energy may be transferred to the moiety via Forster resonance energy transfer. In some cases, these may be contained within a suitable carrier material, for example, a particle or a micelle. Such systems and methods may be used in a variety of applications, including various biological or physical applications. For example, such systems and methods may be useful for delivering drugs or other releasable moieties to regions of the body which may be affected by too much light, such as the eye. Other aspects of the present invention are generally directed to methods for making or using such systems, kits including such systems, or the like. 1. A composition , comprising:a photosensitizer;an annihilator able to accept triplet-triplet energy transfer from the photosensitizer;a cleavable moiety able to accept energy from the annihilator in the higher energy state to cause cleavage of the cleavable moiety; anda releasable moiety releasable from the composition upon cleavage of the cleavable moiety.2. (canceled)3. The composition of claim 1 , wherein the photosensitizer is able to absorb a photon and transfer energy from the photon to the annihilator.4. The composition of claim 1 , wherein the photosensitizer comprises palladium octaethylporphyrin.58-. (canceled)9. The composition of claim 1 , wherein the photosensitizer has an excitation wavelength of between about 360 nm and about 700 nm.1011-. (canceled)12. The ...

Lipid derivative in which hydrophilic polymer is bound through cyclic benzylidene acetal linker

A lipid derivative in which a hydrophilic polymer is bound through a cyclic benzylidene acetal linker, and which can accurately control a hydrolysis rate in the weakly acidic environment of a living body to detach the hydrophilic polymer from a lipid membrane structure. The lipid derivative is represented by formula (1): wherein, R 1 and R 6 are each independently a hydrogen atom or a hydrocarbon group; R 2 , R 3 , R 4 and R 5 are each independently an electron-withdrawing or electron-donating substituent or a hydrogen atom; R 7 is a hydrocarbon group having from 8 to 24 carbon atoms, an acyl group having from 8 to 24 carbon atoms, a cholesterol derivative, a glycerolipid, a phospholipid or a sphingolipid; P is a hydrophilic polymer; s is 1 or 2, t is 0 or 1, and s+t is 1 or 2; and Z 1 and Z 2 are each independently a selected divalent spacer.

BLOCK COPOLYMERS AND SELF-ASSEMBLING NANOPARTICLES FORMED THEREFROM

The subject matter of this invention relates to block copolymers (BCPs) and, more particularly, to block copolymers capable of self-assembly into nanoparticles for the delivery of hydrophobic cargos. The BCPs include a hydrophobic block that contains a thioether functional group that is susceptible to oxidation, transforming the solubility of the block from hydrophobic to hydrophilic, thereby releasing the hydrophobic cargo of the nanoparticle. 1. A method of forming a block copolymer , the method comprising:dissolving in a solvent an amphiphilic diblock copolymer comprising a poly(ethylene oxide) hydrophilic block and a polycarbonate hydrophobic block, the polycarbonate hydrophobic block block including at least one allyl functional group or propargyl functional group;exposing the polymer solution to ultraviolet radiation;adding to the polymer solution one of the following: a quantity of 3-mercaptopropionic acid or a quantity of 1-(2-mercaptoethyl)-3-phenylurea; andprecipitating acid-functionalized diblock polymers from the polymer solution.2. The method of claim 1 , wherein the amphiphilic diblock copolymer is PEG-P(MTC-MAC).3. The method of claim 2 , wherein 3-mercaptopropionic acid is added to the polymer solution.4. The method of claim 2 , wherein 1-(2-mercaptoethyl)-3-phenylurea is added to the polymer solution.5. The method of claim 1 , wherein the amphiphilic diblock copolymer is PEG-P(MTC-MPC).6. The method of claim 5 , wherein 3-mercaptopropionic acid is added to the polymer solution.7. A method of forming a micellar particle claim 5 , the method comprising:dissolving in a first solvent a therapeutic agent; a hydrophilic block; and', 'a hydrophobic block containing at least one functional group selected from a group consisting of: a thioether functional group;, 'dissolving in a second solvent at least one block copolymer comprisingmixing the therapeutic agent solution and the block copolymer solution; andadding the mixed solution to water.8. The method of ...