Composite Nanoparticles And Uses Thereof

Abstract

Provided herein are composite nanoparticles, methods of making composite nanoparticles and methods of using composite nanoparticles to treat or ameliorate various diseases, such as, for example, cancer.

1 . A method for forming composite nanoparticles comprising:
 making subunit nanoparticles of diameter between about 10 nm and about 20 nm which include an active ingredient; and   assembling the subunit nanoparticles into composite nanoparticles of diameter between about 60 nm and about 400 nm.   
     
     
         2 . The method of  claim 1 , wherein the active ingredient is hydrophobic. 
     
     
         3 . The method of  claim 1 , wherein the subunit nanoparticles are made by a method comprising:
 dissolving the drug in aqueous solution;   adding the aqueous solution to an agitated organic polymer solution to form a water-in-oil emulsion;   adding the solution to an excess of water including an emulsifier with agitation to form water-in-oil-in-water emulsion;   removing the organic solvent.   
     
     
         4 . The method of  claim 1 , wherein the subunit nanoparticles are made by a method comprising:
 dissolving the drug in volatile water-miscible solvent to form a solution;   adding the solution to an agitated aqueous solution of carrier polymer to form an oil-in-water emulsion; and   diluting the oil-in-water emulsion with water; and   filtering the solution to collect the nanoparticles.   
     
     
         5 . The method of  claim 1 , wherein the subunit nanoparticles are made by a method comprising:
 dissolving the drug in a water immiscible volatile organic solvent which includes a carrier polymer to form a solution;   adding the solution to an excess of water which includes an emulsifier; and   removing the solvent.   
     
     
         6 . The method of  claim 1 , wherein the subunit nanoparticles are made by a method comprising:
 grafting the drug to a water soluble polymer; and   aggregating the modified polymer.   
     
     
         7 . The method of  claim 1 , wherein the composite nanoparticles are made by a method comprising:
 dispersing the subunit nanoparticles in water;   adding the dispersed nanoparticles to an agitated water immiscible organic solvent which includes a carrier polymer to form a water in oil solution;   adding the water in oil solution to an excess of water which includes an emulsifier; and   removing the solvent.   
     
     
         8 . The method of  claim 1 , wherein the composite nanoparticles are made by a method comprising:
 dissolving the subunit nanoparticles in a water immiscible volatile organic solvent which includes a carrier polymer to form a solution;   adding the solution to an excess of water which includes an emulsifier; and   removing the solvent.   
     
     
         9 . The method of  claim 1 , wherein the composite nanoparticles are crosslinked. 
     
     
         10 . The method of  claim 1 , wherein the composite nanoparticles are made by a method comprising crosslinking subunit nanoparticles. 
     
     
         11 . The method of  claim 1 , wherein the composite nanoparticle decomposes in tumor tissue. 
     
     
         12 . The method of  claim 1 , wherein the composite nanoparticle decomposes below about pH 6.4. 
     
     
         13 . The method of  claim 1 , wherein the composite nanoparticle disintegrates into subunit particles at the pH of the interstitial space of the tumor tissue, wherein the pH of the cancer interstitial space is between 5.6 and 6.4.