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Thermosensitive liposomal cisplatin : formulation development, in vitro characterization and in vivo plasma elimination studies Woo, Janet


Cytotoxic anticancer drugs lack specificity and for this reason, antitumour effects are often associated with severe and sometimes life threatening toxicities. In an effort to improve the specificity and targeting of anticancer drugs, investigators have developed drug carrier formulations. Among the different drug delivery systems designed for intravenous use, liposomes have demonstrated beneficial properties that translate into meaningful improvements in therapeutic activity for many anticancer drugs. Cisplatin is a commonly employed anticancer drug which is nephrotoxic and myelosuppressive. In an effort to minimize the drug associated toxicities, a liposomal drug formulation of cisplatin has been developed for use in clinical trials. The results of these clinical studies; however, were disappointing as the cisplatin formulation demonstrated insignificant therapeutic activity, due in part, to the insufficient release of encapsulated contents following administration. For this reason, the development of a triggered release liposome formulation is desirable. In this report, cisplatin was encapsulated into lysolipid containing thermosensitive liposomes (LTSL) using a novel technique, which relies on the equilibration of cisplatin across the liposomal bilayer at temperatures above the gel-to-liquid phase transition (Tc) of the bulk phospholipid. Mild heating of the LTSL did not engender the presence of any irregular structures as determined by cryo-transmission electron microscopy and interestingly, the drug loaded liposomes were similar in morphology to the empty liposomes. In vitro data demonstrated that >95% of encapsulated cisplatin was released within 5 minutes following mild heating at 42°C while

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