Development and characterization of a novel liposome-based formulation of SN-38

Development and characterization of a novel liposome-based formulation of SN-38
February 11, 2004
By J. Allen Zhang, Tong Xuan, Manjeet Parmar, Lan Ma, Sydney Ugwu, Shahid Ali and Imran Ahmad
International Journal of Pharmaceutics
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Abstract
SN-38, 7-ethyl-10-hydroxycamptothecin, is the active metabolite of Irinotecan (CPT-11), a topoisomerase I inhibitor commercially available as Camptosar?. SN-38 is approximately 200?2000-fold more cytotoxic than CPT-11. Despite its promising anticancer potential, SN-38 thus far has not been used as an anticancer drug due to its poor solubility in any pharmaceutically acceptable solvents. In addition, SN-38 has low affinity to lipid membranes; it tends to precipitate in aqueous phase resulting in a very low drug-to-liposome entrapment. SN-38 also reversibly converts to an inactive open lactone ring structure at physiological pH. We have developed a novel, liposome-based SN-38 formulation (LE-SN-38). The formulation contains liposomes of uniform size distribution (<200 nm), and it is easy-to-use. Drug entrapment efficiency of the formulation is>95%. Long-term stability studies indicate that the lyophilized LE-SN-38 is physically and chemically stable for at least 6 months at 2?8 ?C. In preclinical studies, LE-SN38 has shown promising results in terms of increased cytotoxicity against various tumor cell lines and better therapeutic efficacy towards xenograft mouse models compared to CPT-11.