Immune-modifying nanoparticles for the treatment of inflammatory diseases

Abstract

The current invention involves the administration of negatively charged particles, such as polystyrene, PLGA, or diamond particles, to subjects to ameliorate inflammatory immune responses. Additionally, the present invention describes methods of treating inflammatory diseases by administering these same negatively charged particles.

What is claimed is: 
     
         1 . A composition comprising particles having a negative surface charge, 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 −100 mV to about 0 mV. 
     
     
         2 . The composition of  claim 1 , wherein the polyamino acid having a carboxyl group on the side chain is poly(aspartic acid) or poly(glutamic acid). 
     
     
         3 . The composition of  claim 2 , 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). 
     
     
         4 . The composition of  claim 1 , wherein the particles are microparticles or nanoparticles. 
     
     
         5 . The composition of  claim 1 , wherein the particles have a zeta potential ranging from −75 mV to about 0 mV, or −60 mV to about 0 mV, or −50 mV to about 0 mV, or −40 mV to about 0 mV, or −30 mV to about 0 mV, or −20 mV to about 0 mV, or −10 mV to about 0 mV, or −100 mV to −50 mV, or −75 mV to −50 mV, or −50 mV to −40 mV. 
     
     
         6 . The composition of  claim 1 , wherein the particles have a zeta potential of less than −50 mV. 
     
     
         7 . The composition of  claim 1 , wherein the particles have a zeta potential ranging from −100 mV to −50 mV 
     
     
         8 . The composition of  claim 1 , wherein the PLGA has a molecular weight of 1,000 Da to 100,000 Da. 
     
     
         9 . The composition of  claim 8 , wherein the PLGA has a molecular weight of 12,000 Da to 98,000 Da. 
     
     
         10 . The composition of  claim 9 , wherein the PLGA has a molecular weight of 12,000 Da to 48,000 Da. 
     
     
         11 . The composition of  claim 1 , 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. 
     
     
         12 . The composition of  claim 1 , wherein the PLGA contains multiple negatively charged terminal groups. 
     
     
         13 . The composition of  claim 12 , wherein the multiple negatively charged terminal groups are carboxylate groups. 
     
     
         14 . The composition of  claim 1 , wherein the particles have been modified to comprise one or more carboxyl groups on the particle's surface. 
     
     
         15 . The composition of  claim 1 , wherein the particles have an average diameter of about 0.1 μm to about 10 μm. 
     
     
         16 . The composition of  claim 11 , wherein the particles have an average diameter of about 0.2 μm to about 2 μm. 
     
     
         17 . The composition of  claim 1 , further comprising one or more pharmaceutically acceptable excipients. 
     
     
         18 . The composition of  claim 17 , 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. 
     
     
         19 . The composition of  claim 17 , wherein one of the one or more pharmaceutically acceptable excipients is a surfactant. 
     
     
         20 . The composition of  claim 19 , wherein the surfactant is anionic, cationic, or nonionic. 
     
     
         21 . The composition of  claim 23 , 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). 
     
     
         22 . A composition comprising particles having negative surface charges, 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 −0 mV, and wherein the particles are made by a double emulsion process. 
     
     
         23 . The composition of  claim 22 , wherein the polyamino acid having a carboxyl group on the side chain is poly(aspartic acid) or poly(glutamic acid). 
     
     
         24 . The composition of  claim 23 , 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).