Methods and compositions for synthesis of therapeutic nanoparticles

Abstract

Improved methods and reactants for the chemical synthesis of therapeutic nanoparticles are provided. The nanoparticles comprise a polymeric core, to which is attached one or more homing molecules and one or more therapeutic agents. Improvements in speed, yield and purity are attained using the methods disclosed herein.

What is claimed is: 
     
         1 . A 20-(Boc-aminoacyl) derivative of camptothecin (20-(Boc-aminoacyl)-CPT) having the structure: 
       
         
           
           
               
               
           
         
       
       wherein R is one or more α-carbon atoms of an amino acid optionally bonded to an amino acid functional group. 
     
     
         2 . The 20-(Boc-aminoacyl)-CPT derivative of  claim 1 , wherein the amino acid functional group is selected from functional groups of glycine, valine, alanine, β-alanine, GABA and the dipeptide phenylalanine-glycine. 
     
     
         3 . A 20-(Boc-aminoacyl) derivative of camptothecin (20-(Boc-aminoacyl)-CPT) having the structure: 
       
         
           
           
               
               
           
         
       
       wherein:
 R is an amino acid functional group; 
 n is from 1-4 inclusive; and 
 when n is greater than one, each R can be the same or different. 
 
     
     
         4 . The 20-(Boc-aminoacyl)-CPT derivative of  claim 3 , wherein:
 n is one; and   R is selected from the functional group of
 (a) glycine, 
 (b) alanine, 
 (c) valine, 
 (d) leucine, 
 (e) isoleucine, or 
 (f) phenylalanine 
   
     
     
         5 . The 20-(Boc-aminoacyl)-CPT derivative of  claim 3 , wherein:
 n is two, and   R is selected from the functional groups of:
 (a) glycine and glycine; 
 (b) glycine and phenylalanine; or 
 (c) phenylalanine and glycine. 
   
     
     
         6 . The 20-(Boc-aminoacyl)-CPT derivative of  claim 3 , wherein:
 n is three, and   R is selected from the functional groups of:
 (a) glycine, glycine and glycine; and 
 (b) glycine, phenylalanine and glycine. 
   
     
     
         7 . The 20-(Boc-aminoacyl)-CPT derivative of  claim 3 , wherein:
 n is four, and   R is selected from the functional groups of:
 (a) glycine, glycine, glycine and glycine; 
 (b) glycine, glycine, phenylalanine and glycine; and 
 (c) glycine, phenylalanine, glycine and glycine. 
   
     
     
         8 . A 20-(Boc-aminoacyl) derivative of camptothecin (20-(Boc-aminoacyl)-CPT) having the structure: 
       
         
           
           
               
               
           
         
         wherein:
 m is from 1-5 inclusive. 
 
       
     
     
         9 . The 20-(Boc-aminoacyl)-CPT derivative of  claim 8 , wherein m is 2. 
     
     
         10 . The 20-(Boc-aminoacyl)-CPT derivative of  claim 8 , wherein m is 3. 
     
     
         11 . The 20-(Boc-aminoacyl)-CPT derivative of  claim 8 , wherein m is 4. 
     
     
         12 . The 20-(Boc-aminoacyl)-CPT derivative of  claim 8 , wherein m is 5. 
     
     
         13 . A trifluoroacetate (TFA) salt of a 20-aminoacyl derivative of CPT (20-(TFA·aminoacyl)-CPT) having the structure: 
       
         
           
           
               
               
           
         
       
       wherein R is one or more α-carbon atoms of an amino acid optionally bonded to an amino acid functional group. 
     
     
         14 . The TFA salt of  claim 13 , wherein the amino acid functional group is selected from functional groups of glycine, alanine, β-alanine, valine, GABA and the dipeptide phenylalanine-glycine.