Lipid carrier compositions with enhanced blood stability

Abstract

Liposomes that contain at least 10 mol % of a negatively charged lipid coupled to a non-zwitterionic moiety are stable in the blood. Liposomes containing at least 1 mol % of such lipids may be frozen safely.

1 . A composition comprising liposomes wherein said liposomes comprise at least one vesicle forming lipid; at least 1 mol % of an aggregation preventing agent which is a negatively charged lipid comprising a non-zwitterionic moiety; and at least one biologically active agent and contain less than 20 mol % of cholesterol;
 wherein said liposomes have a mean diameter between 80-200 nm+/−25 nm; and   wherein said liposomes have a transition temperature (T c ) of at least 38° C.   
     
     
         2 . The composition of  claim 1  wherein said liposomes comprise a vesicle-forming lipid containing acyl groups of chain length of at least  18  carbon atoms. 
     
     
         3 . The composition of  claim 1  wherein said aggregation preventing agent is a PEGylated amphipathic lipid or a phosphatidylglycerol (PG) or a phosphatidylinositol (PI). 
     
     
         4 . The composition of  claim 3  wherein said aggregation preventing agent is a PG or a PI. 
     
     
         5 . The composition of  claim 1  wherein said liposomes comprise at least 10 mol % of said aggregation preventing agent. 
     
     
         6 . The composition of  claim 1  wherein said liposomes further contain a cryoprotectant. 
     
     
         7 . The composition of  claim 1  which is cryostable. 
     
     
         8 . The composition of  claim 1  in a frozen or lyophilized form. 
     
     
         9 . The composition of  claim 1  wherein said liposome comprises 10 mol % of a PI or 10 mol % of a PG and wherein said vesicle forming lipid is distearoylphosphatidylcholine. 
     
     
         10 . The composition of  claim 1  wherein said biologically active agent comprises FUDR and/or CPT11 and/or carboplatin. 
     
     
         11 . The composition of  claim 1  which further contains a pharmaceutically acceptable excipient. 
     
     
         12 . A method to administer a biological agent to a subject in need of said agent which method comprises administering to said subject an effective amount of the composition of  claim 1 . 
     
     
         13 . A method to preserve a liposome composition which comprises freezing or lyophilizing the composition of  claim 1 . 
     
     
         14 . A method to preserve a liposome composition which comprises freezing or lyophilizing the composition of  claim 6 . 
     
     
         15 . A method to preserve a liposome composition which comprises freezing or lyophilizing the composition of  claim 7 .