Liposomal antineoplastic drugs and uses thereof

Abstract

This invention relates to liposomal antineoplastic agents (e.g., camptothecin) compositions and methods of using such compositions for treating neoplasia and for inhibiting angiogenesis. The compositions and methods are useful for modulating the plasma circulation half-life of an active agent.

What is claimed is:  
     
         1 . A liposomal formulation comprising: 
 a) a liposome having an active agent encapsulated therein; and    b) an empty liposome.    
     
     
         2 . The liposomal formulation of  claim 1 , wherein the ratio of liposomes containing said active agent to said empty liposomes is from about 1:0.5 to 1:1000.  
     
     
         3 . The liposomal formulation of  claim 2 , wherein the ratio of liposomes containing said active agent to said empty liposomes is from about 1:1 to 1:100.  
     
     
         4 . The liposomal formulation of  claim 3 , wherein the ratio of liposomes containing said active agent to said empty liposomes is from about 1:2 to 1:10.  
     
     
         5 . The liposomal formulation of  claim 4 , wherein the ratio of liposomes containing said active agent to said empty liposomes is from about 1:3 to 1:5.  
     
     
         6 . The liposomal formulation of  claim 1 , wherein said active agent is an antineoplastic drug.  
     
     
         7 . The liposomal formulation of  claim 6 , wherein said antineoplastic drug is a camptothecin.  
     
     
         8 . The liposomal formulation of  claim 7 , wherein said camptothecin is a member selected from the group consisting of irinotecan, topotecan, 9-amino camptothecin, 10,11-methylenedioxy camptothecin, 9-nitro camptothecin, TAS 103,7-(4-methyl-piperazino-methylene)-10,11-ethylenedioxy-20(S)-camptothecin and 7-(2-N-isopropylamino)ethyl)-20(S)-camptothecin.  
     
     
         9 . The liposomal formulation of  claim 8 , wherein said camptothecin is topotecan.  
     
     
         10 . The liposomal formulation of  claim 9 , wherein said antineoplastic drug is a vinca alkaloid.  
     
     
         11 . The liposomal formulation of  claim 10 , wherein said vinca alkaloid is a member selected from the group consisting of vincristine, vinblastine, vinorelbine and vindesine.  
     
     
         12 . The liposomal formulation of  claim 11 , wherein said vinca alkaloid is vincristine.  
     
     
         13 . The liposomal formulation of  claim 11 , wherein said vinca alkaloid is vinorelbine.  
     
     
         14 . The liposomal formulation of  claim 1 , wherein the ratio of said active agent to lipid is about 0.005-1:1 (w/w).  
     
     
         15 . The liposomal formulation of  claim 14 , wherein the ratio of said active agent to lipid is about 0.05-0.9:1 (w/w).  
     
     
         16 . The liposomal formulation of  claim 15 , wherein the ratio of said active agent to lipid is about 0.1-0.5:1 (w/w).  
     
     
         17 . The liposomal formulation of  claim 1 , wherein said active agent comprises free active agent and precipitated active agent.  
     
     
         18 . The liposomal formulation of  claim 17 , wherein at least 50% of said active agent is precipitated active agent.  
     
     
         19 . The liposomal formulation of  claim 1 , wherein said liposomes containing said active agent comprise sphingomyelin.  
     
     
         20 . The liposomal formulation of  claim 19 , further comprising cholesterol.  
     
     
         21 . The liposomal formulation of  claim 20 , wherein the sphingomyelin and cholesterol are present at a molar ratio from 75/25 mol %/mol % sphingomyelin/cholesterol to 30/50 mol %/mol % sphingomyelin/cholesterol.