Liposomes Useful for Drug Delivery

Abstract

The present invention provides liposome compositions containing substituted ammonium and/or polyanion, and optionally with a desired therapeutic or imaging entity. The present invention also provide methods of making the liposome compositions provided by the present invention.

1 . An irinotecan liposome composition comprising irinotecan and a polyphosphorylated polyol encapsulated in a lipid vesicle, wherein the composition is obtainable by a process comprising the steps of:
 (a) forming the lipid vesicle encapsulating the polyphosphorylated polyol and one or more substituted ammonium compounds selected from the group consisting of diethylammonium and triethylammonium in a lipid composition comprising one or more lipid components forming the lipid vesicle;   (b) contacting the lipid vesicle with irinotecan at a temperature above the phase transition temperature of the lipid vesicle, to load at least 85% of the irinotecan into the lipid vesicle.   
     
     
         2 . The irinotecan liposome composition of  claim 1 , wherein the polyphosphorylated polyol has a pKa of 3 or less. 
     
     
         3 . The irinotecan liposome composition of  claim 1 , wherein the lipid vesicle comprises DSPC and cholesterol in a 3:2 molar ratio. 
     
     
         4 . The irinotecan liposome composition of  claim 1 , wherein at least about 70% of the irinotecan remains encapsulated in the lipid vesicle after 8 hours in the blood of a CD-1 mouse. 
     
     
         5 . The irinotecan liposome composition of  claim 1 , wherein the polyphosphorylated polyol is selected from the group consisting of polyphosphorylated: ethyleneglycol, propylene glycol, glycerol, treitol, erythritol, pentaerythritol, ribitol, arabitol, sorbitol, mannitol, lactitol, maltitol, fructitol, glucitol, xylitol, and inositol. 
     
     
         6 . The irinotecan liposome composition of  claim 1 , wherein the polyphosphorylated polyol is an inositol polyphosphate. 
     
     
         7 . The irinotecan liposome composition of  claim 6 , wherein the inositol polyphosphate is inositol hexaphosphate. 
     
     
         8 . An irinotecan liposome composition comprising irinotecan and an inositol polyphosphate encapsulated in a lipid vesicle, wherein the composition is obtainable by a process comprising the steps of:
 (a) forming the lipid vesicle encapsulating the inositol polyphosphate and one or more substituted ammonium compounds selected from the group consisting of diethylammonium and triethylammonium in a lipid composition comprising one or more lipid components forming the lipid vesicle;   (b) contacting the lipid vesicle with irinotecan at a temperature above the phase transition temperature of the lipid vesicle, to load at least 85% of the irinotecan into the lipid vesicle.   
     
     
         9 . The irinotecan liposome composition of  claim 8 , wherein the polyphosphorylated polyol has a pKa of 3 or less. 
     
     
         10 . The irinotecan liposome composition of  claim 8 , wherein the lipid vesicle comprises DSPC and cholesterol in a 3:2 molar ratio. 
     
     
         11 . The irinotecan liposome composition of  claim 8 , wherein at least about 70% of the irinotecan remains encapsulated in the lipid vesicle after 8 hours in the blood of a CD-1 mouse. 
     
     
         12 . The irinotecan liposome composition of  claim 11 , wherein the lipid vesicle comprises DSPC and cholesterol in a 3:2 molar ratio and the polyphosphorylated polyol has a pKa of 3 or less. 
     
     
         13 . The irinotecan liposome composition of  claim 12 , wherein the inositol polyphosphate is inositol hexaphosphate. 
     
     
         14 . The irinotecan liposome composition of  claim 8 , wherein the inositol polyphosphate is inositol hexaphosphate. 
     
     
         15 . The irinotecan liposome composition of  claim 1 , wherein the lipid vesicle encapsulates the polyphosphorylated polyol at a concentration of 1.2-2.5N. 
     
     
         16 . The irinotecan liposome composition of  claim 1 , wherein the lipid vesicle encapsulates one or more substituted ammonium compounds at a concentration of 0.55-0.65M. 
     
     
         17 . The irinotecan liposome composition of  claim 16 , wherein the polyphosphorylated polyol is an inositol polyphosphate. 
     
     
         18 . The irinotecan liposome composition of  claim 17 , wherein the lipid vesicle encapsulates the inositol polyphosphate at a concentration of 1.2-2.5N. 
     
     
         19 . The irinotecan liposome composition of  claim 8 , wherein
 (i) the lipid vesicle encapsulates the polyphosphorylated polyol at a concentration of 1.2-2.5N, or the lipid vesicle encapsulates one or more substituted ammonium compounds at a concentration of 0.55-0.65M; or   (ii) the lipid vesicle encapsulates the polyphosphorylated polyol at a concentration of 1.2-2.5N, and the lipid vesicle encapsulates one or more substituted ammonium compounds at a concentration of 0.55-0.65M.   
     
     
         20 . An irinotecan liposome composition comprising irinotecan and an inositol polyphosphate encapsulated in a lipid vesicle, wherein the composition is obtainable by a process comprising the steps of:
 (a) forming the lipid vesicle encapsulating the inositol polyphosphate at a concentration of 1.2-2.5 N and one or more substituted ammonium compounds selected from the group consisting of diethylammonium and triethylammonium at a concentration of 0.55-0.65 M in a lipid composition comprising DSPC, cholesterol and PEG-DSPE in a 3:2:0.015 molar ratio;   (b) contacting the lipid vesicle with irinotecan at a temperature above the phase transition temperature of the lipid vesicle, to load at least 85% of the irinotecan into the lipid vesicle.