Targeted atherosclerosis treatment

Abstract

This invention relates generally to methods for ameliorating at least one symptom or aspect of atherosclerosis. The methods include administration of targeted carrier compositions comprising a therapeutic agent effective in ameliorating at least one aspect of atherosclerosis coupled to a targeting ligand effective is targeting the therapeutic agent to tissue associated with atherosclerotic plaque.

1 . A method for inhibiting atherosclerotic plaques in a subject which method comprises administering to a subject diagnosed with atherosclerosis, a composition comprising a nanoparticulate carrier contained in an emulsion and an αvβ3 targeting ligand and an anti-angiogenic agent, wherein the targeting ligand and anti-angiogenic agent are coupled through colocalization in said nanoparticles;
 wherein the anti-angiogenic agent is a matrix metalloproteinase inhibitor, a tissue inhibitor of metalloproteinase, fumagillin, TNP470, a statin, a vascular endothelial growth factor (VEGF) inhibitor, a heparinase, an antithrombin-3 fragment, or a fibroblast growth factor (FGF) inhibitor; and 
 wherein said anti-angiogenic agent is effective at a dosage at least 56,000 fold lower than that required when said anti-angiogenic agent is administered as a free drug. 
 
     
     
         2 . The method of  claim 1 , wherein the antiangiogenic agent is a matrix metalloproteinase inhibitor, a tissue inhibitor of metalloproteinase, fumagillin, TNP470, a statin, a heparinase, or an antithrombin-3 fragment. 
     
     
         3 . The method of  claim 1 , wherein the nanoparticulate carrier is a high boiling liquid fluorocarbon coated with lipid/surfactant. 
     
     
         4 . The method of  claim 1 , wherein the administering is systemic. 
     
     
         5 . The method of  claim 4 , wherein the administering is intravenous. 
     
     
         6 . The method of  claim 1 , wherein the targeted carrier further comprises an image contrast agent, and the method further comprises imaging the targeted carrier after administration to the subject. 
     
     
         7 . The method of  claim 1 , wherein said composition is administered to said subject one, two or three times. 
     
     
         8 . A composition comprising a nanoparticulate carrier contained in an emulsion and an α v β 3  targeting ligand and an anti-angiogenic agent, wherein the targeting ligand and anti-angiogenic agent are coupled through colocalization in said nanoparticles;
 wherein the anti-angiogenic agent is a matrix metalloproteinase inhibitor, a tissue inhibitor of metalloproteinase, fumagillin, TNP470, a statin, a vascular endothelial growth factor (VEGF) inhibitor, a heparinase, an antithrombin-3 fragment, or a fibroblast growth factor (FGF) inhibitor; and 
 wherein said anti-angiogenic agent is effective at a dosage at least 56,000 fold lower than that required when said anti-angiogenic agent is administered as a free drug. 
 
     
     
         9 . The composition of  claim 1 , wherein the antiangiogenic agent is a matrix metalloproteinase inhibitor, a tissue inhibitor of metalloproteinase, fumagillin, TNP470, a statin, a heparinase, or an antithrombin-3 fragment. 
     
     
         10 . The composition of  claim 9 , wherein the nanoparticulate carrier is a high boiling liquid fluorocarbon coated with lipid/surfactant.