Nishiyama N, Kataoka K
Department of Materials Science, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
J Control Release. 2001 Jul 6;74(1-3):83-94. doi: 10.1016/s0168-3659(01)00314-5.
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 formation 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 degrees C. 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.
通过顺二氯二氨合铂（II）（顺铂，CDDP）与聚（乙二醇）-聚（α，β-天冬氨酸）嵌段共聚物（PEG-P（Asp））和聚（α，β-天冬氨酸）均聚物（P（Asp））的混合物在蒸馏水中形成聚合物-金属配合物，制备了包封抗肿瘤药物顺铂的尺寸在20至100nm范围内变化的聚合物胶束。P（Asp）与PEG-P（Asp）的比例增加导致胶束尺寸以可控方式增加，同时在37℃生理盐水中胶束衰变的诱导期延长，伴有顺铂的持续释放。所有具有不同P（Asp）掺入率的载顺铂胶束由于长时间孵育导致顺铂从胶束中释放而表现出明显的体外细胞毒性。这些载顺铂胶束有望通过基于EPR效应的体内生物分布调节在顺铂的肿瘤靶向递送系统中具有潜在用途。
