Peptide Conjugated Particles

Abstract

The present invention provides compositions comprising peptide-coupled biodegradable poly(lactide-co-glycolide) (PLG) particles. In particular, PLG particles are surface-functionalized to allow for coupling of peptide molecules to the surface of the particles (e.g., for use in eliciting induction of immunological tolerance).

1 - 24 . (canceled) 
     
     
         25 . A composition comprising particles having a negative surface charge and comprising one or more antigens or allergens conjugated to the surface of the particles or encapsulated within the particle, wherein the particles comprise polylactide-co-glycolide (PLGA) and a polyamino acid having a carboxyl group on the side chain, wherein the particles have a negative zeta potential ranging from about −100 mV to about −30 mV. 
     
     
         26 . The composition of  claim 25 , wherein the polyamino acid having a carboxyl group on the side chain is poly(aspartic acid) or poly(glutamic acid). 
     
     
         27 . The composition of  claim 26 , wherein the polyamino acid having a carboxyl group on the side chain is poly(gamma-glutamic acid), poly(L-glutamic acid), poly(D-glutamic acid), or poly(D,L-glutamic acid). 
     
     
         28 . The composition of  claim 25 , wherein the particles are microparticles or nanoparticles. 
     
     
         29 . The composition of  claim 25 , wherein the particles have a zeta potential ranging from about −80 mV to −30 mV, or about −75 mV to −30 mV, or about −50 mV to −30 mV, or about −100 mV to −50 mV, or about −75 mV to −50 mV, or about −75 mV to −25 mV. 
     
     
         30 . The composition of  claim 25 , wherein the particles have a zeta potential ranging from about −80 mV to −30 mV 
     
     
         31 . The composition of  claim 25 , wherein the PLGA has a molecular weight of 1,000 Da to 100,000 Da. 
     
     
         32 . The composition of  claim 31 , wherein the PLGA has a molecular weight of 12,000 Da to 98,000 Da. 
     
     
         33 . The composition of  claim 32 , wherein the PLGA has a molecular weight of 12,000 Da to 48,000 Da. 
     
     
         34 . The composition of  claim 25 , wherein the PLGA has a lactide: glycolide (L:G) ratio of about 25:75, 30:70, 35:65, 40:60, 45:55, 50:50, 55:45, 60:40, 65:35, 70:30, 75:25, 80:20, 81:19, 82:18, 83:17, 84:16, 85:15, 86:14, 87:13, 88:12, 89:11, 90:10, 91:9, 92:8, 93:7, 94:6, 95:5, 96:4, 97:3, 98:2, 99:1, or 100:0. 
     
     
         35 . The composition of  claim 25 , wherein the PLGA contains multiple negatively charged terminal groups. 
     
     
         36 . The composition of  claim 35 , wherein the multiple negatively charged terminal groups are carboxylate groups. 
     
     
         37 . The composition of  claim 25 , wherein the particles have been modified to comprise one or more carboxyl groups on the particle's surface. 
     
     
         38 . The composition of  claim 25 , wherein the particles have an average diameter of about 0.1 μm to about 10 μm. 
     
     
         39 . The composition of  claim 38 , wherein the particles have an average diameter of about 0.2 μm to about 2 μm. 
     
     
         40 . The composition of  claim 25 , further comprising one or more pharmaceutically acceptable excipients. 
     
     
         41 . The composition of  claim 40 , wherein the one or more pharmaceutically acceptable excipients are selected from the group consisting of preservatives, antioxidants, moisturizers, emollients, buffering agents, solubilizing agents, penetration agents, skin protectants, surfactants, and propellants. 
     
     
         42 . The composition of  claim 40 , wherein one of the one or more pharmaceutically acceptable excipients is a surfactant. 
     
     
         43 . The composition of  claim 42 , wherein the surfactant is anionic, cationic, or nonionic. 
     
     
         44 . The composition of  claim 43 , wherein the surfactant is selected from the group consisting of Polyoxyl 40 Stearate, polysorbate, poloxamers, poloxamine, gelatin, dextran, pluronic L-63, methylcellulose, lecithin, DMAB, polyethylene glycol, polyvinyl alcohol, polyvinylpyyrolidinone, and vitamin E TPGS (D-α-tocopheryl polyethylene glycol 1000 succinate). 
     
     
         45 . A composition comprising particles having negative surface charge and comprising one or more antigens or allergens conjugated to the surface of the particles or encapsulated within the particle, wherein the particles comprise polylactide-co-glycolide (PLGA) and a polyamino acid having a carboxyl groups on the side chain, wherein the particles have a negative zeta potential ranging from −100 mV to −30 mV, and wherein the particles are made by a double emulsion process. 
     
     
         46 . The composition of  claim 45 , wherein the polyamino acid having a carboxyl group on the side chain is poly(aspartic acid) or poly(glutamic acid). 
     
     
         47 . The composition of  claim 46 , wherein the polyamino acid having a carboxyl group on the side chain is poly(gamma-glutamic acid), poly(L-glutamic acid), poly(D-glutamic acid), or poly(D,L-glutamic acid). 
     
     
         48 . The composition of  claim 25 , wherein said antigen comprises an autoimmune antigen, an enzyme for enzyme replacement therapy, an allergen, or a viral protein. 
     
     
         49 . The composition of  claim 48 , wherein said antigen comprises one or more epitopes of myelin basic protein, acetylcholine receptor, endogenous antigen, myelin oligodendrocyte glycoprotein, pancreatic beta-cell antigen, insulin, proinsulin, IGRP, glutamic acid decarboxylase (GAD), collagen type 11, human cartilage gp39, fp30-RAPS, proteolipid protein, fibrillarin, small nucleolar protein, thyroid stimulating factor receptor, histones, glycoprotein gp70, pyruvate dehydrogenase dehydrolipoamide acetyltransferase (PCD-E2), hair follicle antigen, gliadin, human tropomyosin isoform 5, Advate, antihemophilic factor, Kogenate, Eloctate, recombinant factor VIII Fc fusion protein, Refacto, Novo Vila, recombinant factor VII, eptacog alfa, Helixate, Monanine, Coagulation Factor IX, Wilate, Ceredase, Alglucerase, Imiglucerase, Elelso, taliglucerase alfa, Agalsidase beta, I-iduronidase, Acid-glucosidase, iduronate-2-sulfatase, arylsufatase B, or N-acetylgalactosamine-4-sulfatase. 
     
     
         50 . The composition of  claim 25 , wherein the antigen is an antigenic peptide. 
     
     
         51 . The composition of  claim 25 , wherein the allergen comprises: Bahia grass pollen (BaGP), peach allergen Pru p 3, alpha s 1-Caein Milk allergen, Api g 1 celery allergen, Berel Brazil nut allergen, B-Lactoglobulin Milk allergen, Bovine serum albumin, Cor a 1.04 Hazelnut allergen, Ovalbumin Egg allergen, peanut proteins, pet dander proteins, house dust mite allergen Der p 1, or an antigenic epitope thereof. 
     
     
         52 . The composition of  claim 25 , wherein the polyamino acid having a carboxyl group on the side chain is poly(L-aspartic acid), poly(D-aspartic acid), or poly(D,L-aspartic acid). 
     
     
         53 . A method of inducing antigen-specific tolerance in a subject in need thereof comprising administering to the subject a composition of  claim 25 .