Cisplatin-loaded polymer-metal complex micelle with time-modulated decaying property as a novel drug delivery system

Purpose. The pharmacological activity and pharmacokinetics of cisplatin (CD DP)-loaded polymeric micelles were examined to reveal their usefulness as a novel tumor-directed drug carrier system of CDDP. Methods, In biodistribution assay, free CDDP or CDDP-loaded micelles were a dministered intravenously to Lewis lung carcinoma-bearing mice. Antitumor a ctivity and nephrotoxicity were respectively evaluated by the measurement o f tumor size and plasma blood urea nitrogen (BUN) after single bolus i.v. a dministration of each drug. Results. The time profile of the plasma Pt level after the injection of the micelles exhibited a time-modulated disappearance as observed in saline in vitro. The micelles exhibited 5.2- and 4.6-fold higher AUC of Pt in the pl asma and tumor, respectively, with minimal change in the kidney, in compari son with free CDDP. suggesting that prolonged circulation of Pt in circulat ion and specific accumulation in the tumor were achieved utilizing the mice llar drug carrier system. Administration of the micelles at the dose exhibi ting antitumor activity similar to free CDDP did not increase the plasma BU N, whereas free CDDP induced its remarkable increase. Conclusion. CDDP-loaded micelles restrained nephrotoxicity, which is the do se-limiting factor of CDDP, while exhibiting tumor specific accumulation. T hus, CDDP-loaded micelles are expected to be a novel formulation of CDDP fo r clinical use.