Cisplatin‐incorporated Polymeric Micelles Eliminate Nephrotoxicity, While Maintaining Antitumor Activity

cis‐Diamminedichloroplatinum (II) (cisplatin, CDDP), a potent anticancer agent, was bound to the aspartic acid residues of poly(ethylene glycol)‐poly(aspartic acid) (PEG‐P(ASP)) block copolymer by ligand substitution reaction at the platinum atom of CDDP. The polymeric drug thus obtained was observed to form a micelle structure in aqueous medium, showing excellent water solubility. In the present study, in vitro and in vivo antitumor activity against several human tumor cell lines, toxicity and pharmacokinetic characteristics in rodents of CDDP‐incorporated polymeric micelles (CDDP/m) were evaluated in comparison with those of CDDP. In vitro, CDDP/m exhibited 10‐17% of the cytotoxicity of CDDP against human tumor cell lines. CDDP/m given by intravenous (i.v.) injection yielded higher and more sustained serum levels than CDDP. In vivo CDDP/m treatment resulted in higher and more sustained levels in tumor tissue than CDDP, and showed similar antitumor activity to CDDP against MKN 45 human gastric cancer xenograft. CDDP/m treatment caused much less renal damage than CDDP. These results indicate that CDDP/m treatment can reduce CDDP‐induced nephrotoxicity without compromising the anticancer cytotoxicity of CDDP.