Liposomes Useful for Drug Delivery

An irinotecan liposome composition comprising irinotecan and sucrose octasulfate encapsulated in a lipid vesicle, the composition obtainable by a process comprising the steps of:

• (a) forming the lipid vesicle encapsulating the sucrose octasulfate and a substituted ammonium compound in the absence of irinotecan, the substituted ammonium compound having the formula:
• wherein
• N is a an ammonium nitrogen atom;
• one or two of R1, R2, R3, and R4 are H;
• and
• the remaining of R1, R2, R3, and R4 are independently an organic group having not more than 8 carbon atoms, and in totality not more than 18 carbon atoms,
• in a lipid composition comprising 1,2-distearoyl-SN-phosphatidylcholine (DSPC) and cholesterol in a 3:2 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 at a concentration that exceeds the concentration of irinotecan in the composition outside of the lipid vesicle;
• and
• (c) removing from the composition substituted cationic ammonium compound that is not encapsulated within the lipid vesicle.

An irinotecan liposome composition comprising irinotecan and sucrose octasulfate encapsulated in a lipid vesicle, the composition obtainable by a process comprising the steps of:

• (a) forming the lipid vesicle encapsulating the sucrose octasulfate and a substituted cationic ammonium compound in a lipid composition comprising one or more lipid components forming the lipid vesicle having a phase transition temperature,
• wherein the substituted ammonium cation is selected from the group consisting of the ammonium cation of:
• pyrrolidine, piperidine, diisopropylamine, diethylamine, triethylamime, dimethylamine, tert-butylamine, cyclohexylamine, methylamine, ethylamine, propylamine, isopropylamine, N-ethylpiperidine, dicyclohexylamine, N-methylpiperidine, diethylmethylamine, dimethylpropylamine, trimethylamine, piperazine, 2-amino-2-methylpropanol, N,N′-dimethylpiperazine, diethyl-(2-hydroxyethyl)amine, ethanolamine, N-hyrdoxyethylpyrrolidine, diethanolamine, ammonia, dimethyl-(2-hydroxyethyl)amine, morpholine, tris-(hydroxymethyl)-aminomethane, and N-methylglucamine;
• and
• (b) contacting the lipid vesicle with irinotecan at a temperature above the phase transition temperature of the lipid vesicle, to load the irinotecan into the lipid vesicle.