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Research Articles: Therapeutics

Carboplatin nanocapsules: a highly cytotoxic, phospholipid-based formulation of carboplatin

Department of Biochemistry of Membranes, Bijvoet Institute and Institute of Biomembranes, Utrecht University, Utrecht, the Netherlands

Requests for reprints: Irene H.L. Hamelers, Department of Biochemistry of Membranes, Bijvoet Institute and Institute of Biomembranes, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands. Phone: 31-30-2533345; Fax: 31-30-2533969. E-mail: i.h.l.hamelers{at}chem.uu.nl

Platinum-based drugs are widely used in cancer chemotherapy. However, their clinical use is limited by systemic toxicity, rapid blood clearance, and the occurrence of resistance. Our research is aimed at increasing the therapeutic index of these drugs by encapsulation in a lipid formulation. Previously, we developed a method for efficient encapsulation of cisplatin in a lipid formulation, yielding cisplatin nanocapsules. Here, we show that carboplatin, a cisplatin-derived anticancer drug with different chemical properties, can be efficiently encapsulated in a lipid formulation by a similar method. The carboplatin nanocapsules exhibit a very high cytotoxicity in vitro: the IC₅₀ value of carboplatin nanocapsules is up to a 1,000-fold lower than that of conventional carboplatin when tested on a panel of carcinoma cell lines. Cellular platinum content analysis and confocal fluorescent imaging of the interaction of the carboplatin nanocapsules with IGROV-1 cells indicate that the improved cytotoxicity is due to increased platinum accumulation in the cells, resulting from uptake of the formulation by endocytosis. [Mol Cancer Ther 2006;5(8):2007–12]

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Received 2/16/06; revised 5/ 2/06; accepted 6/ 7/06.