Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 93, Issue 7, Pages 1718-1724Publisher
ELSEVIER SCIENCE INC
DOI: 10.1002/jps.20086
Keywords
cisplatin; multivesicular liposomes; S180 tumor; sustained release; pharmacokinetics; therapeutic efficacy
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Cisplatin was encapsulated into multivesicular liposomes (MVLs) and the entrapment efficiency, size distribution, and in vitro drug release characteristics of the cisplatin-MVLs were studied. Pharmacokinetics, tissue distribution, and therapeutic efficacy of cisplatin-MVLs were compared against injection of cisplatin solution into mice inoculated with the murine carcinoma 180 (S180) tumor. The results showed that the cisplatin-MVLs were capable of high drug loading (0.1.48:1 mg cisplatin/mg lipid) and high encapsulation efficiency (>80%). The mean diameter of cisplatin-MVLs was 17 pm. In vitro studies of cisplatin-MVLs in saline solution showed that they sustained release of encapsulated drug for >7 days. Cisplatin-MVLs showed higher drug accumulation in the liver, spleen, and tumor regions than cisplatin solution, as well as higher plasma concentrations and a longer circulation time. The therapeutic efficacy of the cisplatin-MVL preparation against S180 tumor-bearing mice is significantly higher than that of cisplatin solution. (C) 2004 Wiley-Liss, Inc. and the American Pharmacists Association.
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