Therapeutic Inhibitor of Vascular Smooth Muscle Cells

Abstract

Methods are provided for inhibiting stenosis following vascular trauma or disease in a mammalian host, comprising administering to the host a therapeutically effective dosage of a therapeutic conjugate containing a vascular smooth muscle binding protein that associates in a specific manner with a cell surface of the vascular smooth muscle cell, coupled to a therapeutic agent dosage form that inhibits a cellular activity of the muscle cell. Methods are also provided for the direct and/or targeted delivery of therapeutic agents to vascular smooth muscle cells that cause a dilation and fixation of the vascular lumen by inhibiting smooth muscle cell contraction, thereby constituting a biological stent.

1 . A method for maintaining vessel luminal area following vascular trauma, comprising: administering to a mammal an intravascular stent comprising an agent that inhibits vascular smooth muscle cell proliferation or migration in a cytostatic amount that has a minimal effect on protein synthesis and allows for vascular repair. 
     
     
         2 . The method of  claim 1 , wherein the agent is a sustained release dosage form. 
     
     
         3 . The method of  claim 2 , wherein the sustained release dosage form comprises microparticles or nanoparticles. 
     
     
         4 . The method of  claim 2 , wherein the sustained release dosage form comprises biodegradable microparticles, biodegradable nanoparticles or a mixture thereof. 
     
     
         5 . The method of  claim 1 , wherein the agent is a cytoskeletal inhibitor. 
     
     
         6 . The method of  claim 1 , wherein the agent comprises a cytochalasin or a cytochalasin analog. 
     
     
         7 . The method of  claim 1 , wherein the agent comprises taxol or a taxol analog. 
     
     
         8 . The method of claim. 1, wherein the cytostatic amount of the agent does not exhibit substantial cytotoxicity. 
     
     
         9 . The method of  claim 1 , wherein the administration inhibits vessel stenosis or restenosis. 
     
     
         10 . The method of  claim 1 , wherein the administration is local. 
     
     
         11 . A method for maintaining vessel luminal area, comprising: administering to a mammalian vessel an intravascular stent comprising an agent that inhibits vascular smooth muscle cell proliferation or migration in a cytostatic amount which allows for cellular repair and extracellular matrix production. 
     
     
         12 . The method of  claim 11 , wherein the agent is a sustained release dosage form. 
     
     
         13 . The method of  claim 12 , wherein the sustained release dosage form comprises microparticles or nanoparticles. 
     
     
         14 . The method of  claim 12 , wherein the sustained release dosage form comprises biodegradable microparticles, biodegradable nanoparticles or a mixture thereof. 
     
     
         15 . The method of  claim 11 , wherein the agent is a cytoskeletal inhibitor. 
     
     
         16 . The method of  claim 11 , wherein the agent comprises a cytochalasin or a cytochalasin analog. 
     
     
         17 . The method of  claim 11 , wherein the agent comprises taxol or a taxol analog. 
     
     
         18 . The method of  claim 11 , wherein the cytostatic amount of the agent does not exhibit substantial cytotoxicity. 
     
     
         19 . The method of  claim 11 , wherein the administration inhibits vessel stenosis or restenosis. 
     
     
         20 . The method of  claim 11 , wherein the administration is local.