Liposomal camptothecin formulations also comprising at least one phospholipid

摘要

A liposome comprises at least one phospholipid and 7-(4-methylpiperazinomethylene)-10,11-ethylenedioxy-20(S)-camptothecin. The liposome may further comprise cholesterol. The liposome can encapsulate camptothecin wherein the liposome is comprised of hydrogenated soy phosphatidylcholine (HSPC) and cholesterol. The HSPC:cholesterol are in a molar ratio of about 2:1 and the lipid:camptothecin molar ratio is from 10:1 to 40:1. The liposome is unilamellar with an average size of less than 100nm The liposome can be produced by forming a lipid film or powder comprised of phosphatidylcholine and cholesterol, hydrating the lipid film or powder with an aqueous buffer containing a counterion solution. Applying a shearing force to obtain liposomes that are unilamellar and less than 100nm. Then 7-(4-methylpiperazinomethylene)-10,11-ethylenedioxy-20(S)-camptothecin is added to the aqueous medium. A gradient is generated between the aqueous medium inside the liposome and the aqueous medium external to the liposome whereby the gradient causes the 7-(4-methylpiperazinomethylene)-10,11-ethylenedioxy-20(S)-camptothecin to load into the liposome. The gradient may be a pH gradient. Further a membrane permeable amine may be added to the aqueous medium external to the liposome whereby the pH of the aqueous inside the liposome is decreased. The liposomes may be used in a pharmaceutical composition for inhibiting the growth of a tumor.