Apoptosis-Modulating Protein Therapy for Proliferative Disorders and Nanoparticles Containing the Same

Abstract

Protein containing nanoparticles and methods of use thereof for the treatment of proliferative disorders are disclosed.

1 . A method for inhibiting restenosis of a blood vessel comprising administering an effective amount of a protein containing nanoparticle via said blood vessel to a subject in need of treatment, thereby inhibiting restenosis in said blood vessel. 
     
     
         2 . The method of  claim 1 , wherein said protein is selected from the group consisting of p21, p27, p53, p63, p73, or a functional fragment thereof. 
     
     
         3 . The method of  claim 2 , wherein said protein is selected from the group of Table I or Table II. 
     
     
         4 . The method of  claim 1 , wherein the nanoparticle comprises a biodegradable polymer comprising a poly(lactide-co-glycolide), poly(lactic acid), poly(alkylene glycol), polybutylcyanoacrylate, poly(methylmethacrylate-co-methacrylic acid), poly-allylamine, polyanhydride, polyhydroxybutyric acid, or a polyorthoester or a combination thereof. 
     
     
         5 . The method of  claim 1 , wherein the nanoparticle further comprises a targeting moiety. 
     
     
         6 . The method of  claim 1 , wherein said blood vessel is an artery and is selected from the group consisting of carotid, coronary, femoral, renal, and cerebral. 
     
     
         7 . The method of  claim 1 , wherein the nanoparticle further comprises a plasticizer to facilitate sustained release of an antioxidant. 
     
     
         8 . The method of  claim 7 , wherein the plasticizer comprises L-tartaric acid dimethyl ester, triethyl citrate, or glyceryl triacetate. 
     
     
         9 . A p53 protein nanoparticle formulation for sustained release of an effective amount of p53 protein said formulation comprising p53 protein, at least one biodegradable polymer, and an inert plasticizer. 
     
     
         10 . The formulation of  claim 9 , further comprising at least one agent selected from the group consisting of an antioxidant, an anti-infective, an antiseptic, a steroid, a therapeutic peptide, an analgesic, an anti-inflammatory agent, an anticancer agent, a narcotic, an anesthetic, an antiangiogenic agent, a polysaccharide, a vaccine, an antigen, or a nucleic acid. 
     
     
         11 . The formulation of  claim 9 , wherein the biodegradable polymer comprises a poly(lactide-co-glycolide), poly(lactic acid), poly(alkylene glycol), polybutylcyanoacrylate, poly(methylmethacrylate-co-methacrylic acid), poly-allylamine, polyanhydride, polyhydroxybutyric acid, or a polyorthoester. 
     
     
         12 . The formulation of  claim 9 , wherein the plasticizer comprises L-tartaric acid dimethyl ester, triethyl citrate, or glyceryl triacetate. 
     
     
         13 . The formulation of  claim 9 , wherein the nanoparticle further comprises a targeting moiety. 
     
     
         14 . A method of managing VSMC inflammation in a patient following angioplasty comprising administering to said patient a therapeutic agent in an effective amount to manage VSMC inflammation. 
     
     
         15 . The method of  claim 14 , wherein said therapeutic agent is a protein containing nanoparticle formulation. 
     
     
         16 . The method of  claim 15 , wherein said protein containing nanoparticle formulation contains a protein or protein fragment set forth in Table I or Table II. 
     
     
         17 . A protein containing nanoparticle formulation wherein said protein is selected from the group consisting of SEQ ID NO: 1-28 in a pharmaceutically acceptable carrier. 
     
     
         18 . A method of inhibiting inflammation in a patient following angioplasty comprising administering to said patient a protein containing nanoparticle formulation comprising a protein or protein fragment selected from the group consisting of SEQ ID NO: 1-28, thereby inhibiting inflammation in said patient.