Sustained release of cisplatin from multivesicular liposomes: potentiation of antitumor efficacy against S180 murine carcinoma.
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 (0.148:1 mg cisplatin/mg lipid) and high encapsulation efficiency (>80%). The mean diameter of cisplatin-MVLs was 17 microm. 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.
Xiao
Chaoju
C
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China.
Qi
Xianrong
X
Maitani
Yoshie
Y
Nagai
Tsuneji
T
D000277:Adjuvants, Pharmaceutic / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D015552:Injections, Intralesional; D008081:Liposomes; D008297:Male; D051379:Mice
D000277:Adjuvants, Pharmaceutic; D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D008081:Liposomes; D002945:Cisplatin