Sustained-release nanoparticle compositions and methods for using the same

Abstract

The present invention is a composition composed of a therapeutic agent encapsulated in a copolymer of an N-alkylacrylamide, a vinyl monomer, and a polyethylene glycol (PEG) conjugate and a method for using the same in the treatment or prevention of a disease or condition.

1 .- 3 . (canceled) 
     
     
         4 . A sustained-release composition in nanoparticle form consisting essentially of a therapeutic agent and a cross-linked copolymer of an N-alkylacrylamide selected from the group consisting of N-methyl-N-n-propylacrylamide, N-methyl-N-isopropylacrylamide, N-propylmethacrylamide, N-isopropylacrylamide, N-N-diethylacrylamide, N-isopropylmethacrylamide, N-cyclopropylacrylamide, N-ethyl-methacrylamide, N-methyl-N-ethylacrylamide, N-cyclopropylmethacrylamide and N-ethylacrylamide, a vinyl monbomer selected from the group consisting of a vinyl alcohol, a vinyl ether, a vinyl ester, vinyl pyrrolidone and a combination of said vinyl monomers, and PEGylated maleic acid conjugate, wherein the weight per weight ratio of the N-alkylacrylamide, vinyl monomer and PEGylated maleic acid conjugate is 70-90:9-20:1-10, said therapeutic agent being encapsulated in said copolymer in an amount from 3% to 10% based on said nanoparticle weight. 
     
     
         5 . The sustained-release nanoparticle composition of  claim 4 , wherein said therapeutic agent is selected from the group consisting of antibiotics, antirestenotics, anti-proliferative agents, anti-neoplastic agents, chemotherapeutic agents, cardiovascular agents, anti-inflammatory agents, immunosuppressive agents, anti-apoptotic and anti-tissue damage agents. 
     
     
         6 . The sustained-release nanoparticle composition of  claim 4 , wherein said therapeutic agent comprises an anti-proliferative agent. 
     
     
         7 . The sustained-release nanoparticle composition of  claim 4 , wherein said ratio is 80:15:5. 
     
     
         8 . The sustained-release nanoparticle composition of  claim 4 , wherein said nanoparticles have an average diameter in the range of 20 nm to 100 nm as measured by transmission electron microscopy. 
     
     
         9 . The sustained-release nanoparticle composition of  claim 4 , wherein said therapeutic agent is an anti-apoptotic agent. 
     
     
         10 . The sustained-release nanoparticle composition of  claim 9 , wherein said anti-apoptotic agent is selected from the group consisting of galectin-3, (-)deprenyl, rapamycin, quercetin and a monoamine oxidase inhibitor. 
     
     
         11 . The sustained-release nanoparticle composition of  claim 4 , wherein said therapeutic agent is rapamycin. 
     
     
         12 . A method for localized delivery of a therapeutic agent to a target site in a patient, said method comprising administering to said target site a therapeutically effective amount of the sustained-release nanoparticle composition as claimed in  claim 4 . 
     
     
         13 . The method of  claim 12 , wherein said nanoparticle composition is administered percutaneously. 
     
     
         14 . The method of  claim 13 , wherein administration of said nanoparticle composition is performed using a needle. 
     
     
         15 . The method of  claim 13 , wherein administration of said nanoparticle composition is performed using a catheter. 
     
     
         16 . The method of  claim 15 , wherein said catheter is a balloon angioplasty catheter. 
     
     
         17 . The method of  claim 12 , wherein said patient is a patient that has undergone intervention to relieve an arterial obstruction. 
     
     
         18 . The method of  claim 17 , wherein said intervention is selected from the group consisting of angioplasty, atherectomy and stenting. 
     
     
         19 . The method of  claim 12 , wherein said target site is a site of cardiovascular disease. 
     
     
         20 . The method of  claim 19 , wherein said cardiovascular disease is a disease of the carotid, coronary, iliac, common femoral, superficial femoral, and popliteal arteries. 
     
     
         21 . The method of  claim 12 , wherein said nanoparticle composition is administered at a site of graft anastomosis. 
     
     
         22 . The method of  claim 12 , wherein the nanoparticle composition administered to said site comprises a therapeutic agent selected from the group consisting of antibiotics, antirestonotics, anti-proliferative agents, anti-neoplastic agents, chemotherapeutic agents, cardiovascular agents, anti-inflammatory agents, immunosuppressive agents, anti-apoptotic and anti-tissue damage agents. 
     
     
         23 . The method of  claim 22 , wherein said therapeutic agent is selected from the group consisting of rapamycin, everolimus and tacrolimus. 
     
     
         24 . The method of  claim 22 , wherein said therapeutic agent comprises a taxane. 
     
     
         25 . The method of  claim 24 , wherein said taxane is paclitaxel.