title: Development and characterization of a novel liposome-based formulation of SN-38.
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 (<200nm), 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 degrees 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.
authors.affiliation: Research & Development, NeoPharm, Inc., Waukegan, IL 60085, USA.
authors.forename: J Allen
authors.initials: JA
authors.lastname: Zhang
authors.forename: Tong
authors.initials: T
authors.lastname: Xuan
authors.forename: Manjeet
authors.initials: M
authors.lastname: Parmar
authors.forename: Lan
authors.initials: L
authors.lastname: Ma
authors.forename: Sydney
authors.initials: S
authors.lastname: Ugwu
authors.forename: Shahid
authors.initials: S
authors.lastname: Ali
authors.forename: Imran
authors.initials: I
authors.lastname: Ahmad
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005260:Female; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D000077146:Irinotecan; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy; D013997:Time Factors; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D000077146:Irinotecan; D002166:Camptothecin