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 .- 79 . (canceled) 
     
     
         80 . A method of maintaining vessel luminal area, comprising administering to a blood vessel a sustained release dosage form comprising a cytostatic amount of taxol or a taxol analog effective to inhibit or reduce stenosis or restenosis of a blood vessel, wherein the cytostatic amount of taxol or taxol analog is an amount that exerts minimal protein synthesis inhibition and cytotoxicity on vascular smooth muscle cells. 
     
     
         81 . The method of  claim 80 , wherein the cytostatic amount of taxol or taxol analog further exerts significant DNA synthesis inhibition on the vascular smooth muscle cells. 
     
     
         82 . The method of  claim 80 , wherein the cytostatic amount of taxol or taxol analog is effective to inhibit vascular smooth muscle cell proliferation. 
     
     
         83 . The method of  claim 80 , wherein the sustained release dosage form is in the form of microparticles, nanoparticles, or a mixture thereof. 
     
     
         84 . The method of  claim 83 , wherein the microparticles, nanoparticles, or a mixture thereof are biodegradable. 
     
     
         85 . The method of  claim 80 , wherein the sustained release dosage form comprises a thermoplastic polyester. 
     
     
         86 . The method of  claim 85 , wherein the thermoplastic polyester comprises polylactide, polyglycolide, or a copolymer comprising lactide and glycolide components. 
     
     
         87 . The method of  claim 80 , wherein the cytostatic amount of the sustained release dosage form does not exhibit substantial cytotoxicity. 
     
     
         88 . The method of  claim 80 , wherein the sustained release dosage form comprises a biodegradable coating or a porous non-biodegradable coating comprising taxol or taxol analog. 
     
     
         89 . The method of  claim 80 , wherein the sustained release dosage form is administered via a catheter. 
     
     
         90 . The method of  claim 89 , wherein the catheter comprises an infusion catheter. 
     
     
         91 . A method of maintaining vessel luminal area, comprising administering to a blood vessel a medical device comprising a sustained release dosage form comprising a cytostatic amount of taxol or a taxol analog effective to inhibit or reduce stenosis or restenosis upon placement of the device, wherein the cytostatic amount of taxol or taxol analog is an amount that exerts minimal protein synthesis inhibition and cytotoxicity on vascular smooth muscle cells. 
     
     
         92 . A sustained release dosage form comprising a cytostatic amount of taxol or a taxol analog effective to inhibit or reduce stenosis or restenosis of a blood vessel, wherein the cytostatic amount of taxol or taxol analog is an amount that exerts minimal protein synthesis inhibition and cytotoxicity on vascular smooth muscle cells. 
     
     
         93 . The sustained release dosage form of  claim 92 , wherein the cytostatic amount of taxol or taxol analog further exerts significant DNA synthesis inhibition on the vascular smooth muscle cells. 
     
     
         94 . The sustained release dosage form of  claim 92 , wherein the cytostatic amount of taxol or taxol analog is effective to inhibit vascular smooth muscle cell proliferation. 
     
     
         95 . The sustained release dosage form of  claim 92 , wherein the sustained release dosage form is in the form of microparticles, nanoparticles, or a mixture thereof 
     
     
         96 . The sustained release dosage form of  claim 95 , wherein the microparticles, nanoparticles, or a mixture thereof are biodegradable. 
     
     
         97 . The sustained release dosage form of  claim 96 , wherein the sustained release dosage form comprises a thermoplastic polyester. 
     
     
         98 . The sustained release dosage form of  claim 97 , wherein the thermoplastic polyester comprises polylactide, polyglycolide, or a copolymer of lactide and glycolide components. 
     
     
         99 . The sustained release dosage form  claim 92 , wherein the amount of taxol or a taxol analog is sufficient to achieve a 10 −3  to 10 −12  M concentration of taxol or taxol analog in the blood vessel, following administration of the sustained release dosage form in the blood vessel. 
     
     
         100 . The sustained release dosage form of  claim 92 , wherein sustained release dosage form is capable of being administered to a blood vessel via a catheter. 
     
     
         101 . The sustained release dosage form of  claim 100 , wherein the catheter comprises an infusion catheter.