Intravascular delivery of nanoparticle compositions and uses thereof

Abstract

The present invention provides methods of delivering a composition comprising nanoparticles that comprise a macrolide and an albumin by directly injecting the nanoparticle composition into the blood vessel wall or the tissue surrounding the blood vessel wall. The methods can be used for inhibiting negative remodeling or vascular fibrosis in the blood vessel and are useful for treating various diseases.

1 . A method of inhibiting vascular fibrosis in a blood vessel in an individual in need thereof, comprising injecting into the blood vessel wall or tissue surrounding the blood vessel wall an effective amount of a composition comprising nanoparticles comprising rapamycin and an albumin. 
     
     
         2 . The method of  claim 1 , wherein the vascular fibrosis is medial vascular fibrosis or adventitial fibrosis. 
     
     
         3 . The method of  claim 1 , wherein the blood vessel is an artery. 
     
     
         4 . The method of  claim 3 , wherein the artery is a coronary artery or a peripheral artery. 
     
     
         5 . The method of  claim 3 , wherein the artery is selected from the group consisting of renal artery, cerebral artery, pulmonary artery, and artery in the leg. 
     
     
         6 . The method of  claim 1 , wherein the nanoparticle composition is injected into the blood vessel wall. 
     
     
         7 . The method of  claim 1 , wherein the nanoparticle composition is injected into the tissue surrounding the blood vessel wall. 
     
     
         8 . The method of  claim 7 , wherein the nanoparticle composition is injected into the adventitial tissue of the blood vessel. 
     
     
         9 . The method of  claim 1 , wherein the nanoparticle composition is injected at a dose of about 0.001 mg to about 100 mg. 
     
     
         10 . The method of  claim 9 , where the nanoparticle composition is injected at a dose of about 0.05 mg to about 5 mg. 
     
     
         11 . The method of  claim 1 , wherein the injection volume of the nanoparticle composition is about 0.01 ml to about 50 ml. 
     
     
         12 . The method of  claim 11 , wherein the injection volume of the nanoparticle composition is about 0.5 ml to about 5 ml. 
     
     
         13 . The method of  claim 1 , wherein the nanoparticle composition is injected though a catheter with a needle. 
     
     
         14 . The method of  claim 1 , wherein the nanoparticle composition is injected distal or proximal to the disease site. 
     
     
         15 . The method of  claim 1 , wherein the nanoparticle composition is injected at least about 2 cm away from the disease site. 
     
     
         16 . The method of  claim 1 , wherein the nanoparticle composition is injected at or adjacent to the disease site. 
     
     
         17 . The method of  claim 1 , wherein the individual has any one of: angina, myocardial infarction, congestive heart failure, cardiac arrhythmia, peripheral artery disease, claudication, or chronic limb ischemia. 
     
     
         18 . A method of promoting positive remodeling in a blood vessel in an individual in need thereof, comprising injecting into the blood vessel wall or tissue surrounding the blood vessel wall an effective amount of a composition comprising nanoparticles comprising rapamycin and an albumin. 
     
     
         19 . A catheter with a needle, wherein the needle contains a composition comprising nanoparticles comprising a macrolide and an albumin, wherein the needle is deployable and can be advanced intravascularly through a blood vessel wall.