title: Preparation, Characterization, and Antitumor Activities of Miriplatin-Loaded Liposomes.
abstract: Because of the insolubility of miriplatin in water, miriplatin and lipiodol suspension is the sole formulation of miriplatin approved in Japan to treat hepatocellular carcinoma by transcatheter arterial chemoembolization. Until now, there have been no reports of other pharmaceutical formulations of miriplatin except miriplatin/lipiodol suspension. In this study, we aimed not only to develop miriplatin-loaded liposomes (lipomiriplatins) which could be administrated systematically for tumors besides hepatocellular carcinoma but also to ascertain whether miriplatin, like its analog of NDDP, was a liposome-dependent antitumor agent. We found that miriplatin could be successfully incorporated into liposomes, and both the stability and antitumor activity of lipomiriplatins were independent of the liposomal compositions. Especially, HPLC was successfully established as the quantitative method for lipomiriplatins, which completely eliminated the interference of cholesterol. Lipomiriplatins possessed favorable colloidal properties (99.71 ± 0.56 nm, -50 mV), high drug-loading capacity (about 2.2 mg/mL), excellent entrapment efficiency (>95%), and robust stability. The remarkable antitumor activities of lipomiriplatin were proved to be mediated by inducing cell apoptosis and were comparable to that of the commercial cisplatin and oxaliplatin injections, indicating that lipomiriplatins showed great promise for future potential clinical application via systematic administration.
authors: Pharmaceutics Department, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, PR China.
authors: Shan
authors: S
authors: Liu
authors: Pharmaceutics Department, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, PR China.
authors: Yunfei
authors: Y
authors: Li
authors: Pharmaceutics Department, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, PR China.
authors: Xiaowei
authors: X
authors: Wang
authors: Pharmaceutics Department, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, PR China.
authors: Jianan
authors: J
authors: Ma
authors: Pharmaceutics Department, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, PR China.
authors: Lili
authors: L
authors: Zhang
authors: Pharmaceutics Department, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, PR China. Electronic address: xiaguimin@126.com.
authors: Guimin
authors: G
authors: Xia
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding; D004355:Drug Stability; D004356:Drug Storage; D006801:Humans; D008081:Liposomes; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000737:chemistry* / Q000494:pharmacology; D010316:Particle Size; D012995:Solubility; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D009944:Organoplatinum Compounds; C406530:miriplatin
keywords: DMPG; HPLC; anti-tumor activity; liposome; miriplatin; preparation