Preparation and characterization of size-controlled polymeric micelle containing cis-dichlorodiammineplatinum(II) in the core

Polymeric micelles of varying size in the range of 20 to 100 nm entrapping an antitumor drug, cis-dichlorodiammineplatinum(II) (cisplatin, CDDP), were prepared through the polymer-metal complex fort-nation of CDDP with a mixture of poly(ethylene glycol)-poly(alpha,beta -aspartic acid) block copolymer (PEG-P(Asp)) and poly(alpha,beta -aspartic acid) homopolymer (P(Asp)) with the different feed ratio in distilled water. An increased ratio of P(Asp) to PEG-P(Asp) led to an increase in the micellar size in a controllable manner as well as prolongation in the induction period of the micellar decay accompanied by a sustained release of CDDP in physiological saline at 37 degreesC. All of the CDDP-loaded micelles with a different incorporation ratio of P(Asp) exhibited appreciable in vitro cytotoxicity due to CDDP release from the micelles by prolonged incubation. These CDDP-loaded micelles are expected to have potential utility in tumor-directed delivery system of CDDP through the modulated in vivo biodisposition based on the EPR effect. (C) 2001 Elsevier Science B.V. All rights reserved.