Blood vessel permeability-enhancement for the treatment of vascular diseases

Abstract

This invention relates to methods of enhancing the permeability of blood vessels to therapeutic agents.

What is claimed: 
     
         1 . A method of treating a vascular disease, comprising:
 providing an implantable medical device;   advancing the implantable medical device to a locale of interest in a vessel of a patient;   administering a permeability-enhancing composition from the implantable medical device to the locale of interest, wherein:
 the permeability-enhancing composition physiochemically interacts with at least one component of endothelial cells or extracellular matrix; and 
   a therapeutic agent is administered as a component of the permeability-enhancing composition or concomitantly with but separately from the permeability-enhancing composition.   
     
     
         2 . The method of  claim 1 , wherein the permeability-enhancing composition comprises a saponin, a semi-synthetic saponin, DS-1, DS-1(R), DS-2 or QH-957. 
     
     
         3 . The method of  claim 1 , wherein the permeability-enhancing composition comprises hyaluronidase, recombinant hyaluronidase or rHuPH2O. 
     
     
         4 . The method of  claim 1 , wherein the implantable medical device comprises a stent. 
     
     
         5 . The method of  claim 1 , wherein the therapeutic agent comprises a particulate carrier. 
     
     
         6 . The method of  claim 5 , wherein the particulate carrier comprises a nanoparticle, a micelle, a worm micelle, a liposome or a polymersome. 
     
     
         7 . The method of  claim 6 , wherein the nanoparticle, micelle, worm micelle, liposome or polymersome further comprises the permeability-enhancing composition. 
     
     
         8 . The method of  claim 7 , wherein the permeability enhancing composition independently comprises a separate particulate carrier from that the therapeutic agent comprises, the particulate carrier being independently selected from the group consisting of a nanoparticle, a micelle, a worm micelle, a liposome or a polymersome. 
     
     
         9 . The method of  claim 6 , wherein the nanoparticle, micelle, worm micelle, liposome or polymersome further comprises a targeting component disposed on its surface and, further, the permeability-enhancing composition is likewise disposed on its surface. 
     
     
         10 . The method of  claim 9 , wherein the nanoparticle, micelle, worm micelle, liposome or polymersome further comprises a targeting component disposed on its surface and, further, the permeability-enhancing composition is likewise disposed on its surface. 
     
     
         11 . The method of  claim 1 , wherein the locale of interest comprises an atherosclerotic lesion, a restenotic lesion, a suspected vulnerable plaque, a vulnerable plaque or a peripheral arterial lesion.