A novel liposomal formulation of cisplatin (L-CDDP) was synthesized and characterized. The L-CDDP was formed by conjugating CDDP to the carboxyl of oleic acid incorporated into empty liposomes. Particle size (155.4±16.1nm) and zeta potential (-50.92±1.19mV) of the L-CDDP were determined. In addition, pharmacokinetic properties and antitumor activity in vitro and in vivo were evaluated. Pharmacokinetic study demonstrated that L-CDDP had markedly prolonged circulation time relative to the free drug. Furthermore, L-CDDP showed significantly enhanced in vitro cytotoxicity in comparison to free CDDP. A549-engrafted mice treated with L-CDDP had a higher survival rate compared to those treated with free CDDP. Finally, A549-engrafted mice treated with L-CDDP showed no significant loss of body weight, whereas free CDDP treatment at the same dose caused significant loss of body weight. These results suggest further evaluation of the in vivo antitumor efficacy of the novel L-CDDP formulation is warranted.
Keywords: Antitumor activity; Cisplatin; Liposomes; Oleic acid; Pharmacokinetics.
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