Cisplatin incorporated in microspheres: development and fundamental studies for its clinical application
Cisplatin incorporated in microspheres: development and fundamental studies for its clinical application
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DOI：
10.1016/s0168-3659(03)00131-7
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发表时间：
2003-05-20
影响因子：
10.8
通讯作者：
Hagiwara, A
中科院分区：
文献类型：
--
作者：
Fujiyama, J;Nakase, Y;Hagiwara, A
一种新的给药制剂，可生物降解的羟基乙酸-乳酸共聚物（PGLA）微球纳入顺铂（CDDP-MS）已被开发用于治疗腹膜癌转移。扫描电镜显示，CDDP-MS表面光滑，空腔内有少量顺铂晶体。电子探针显微分析表明顺铂主要以分子状态存在于基质中。微球的体外释药曲线表明，初始突释率为21.2%，其余药物在14天内缓慢释放。在14天期间，CDDP-MS的水解进展非常缓慢，但在SEM视图中没有形态变化。通过气相色谱法测定，在47 ℃的蒸发温度下，CDDP-MS中截留的二甲基甲酰胺含量为136 ppm。通过Litchfield-Wilcoxon方法计算的CDDP-MS的50%致死剂量值降低至顺铂溶液的57%。对患有腹膜癌病的小鼠的治疗实验表明，与相同剂量的顺铂水溶液相比，CDDP-MS没有增强治疗效果，但由于毒性较小，在CDDP-MS的情况下可以给予大量顺铂。(C)2003 Elsevier Science B. V.保留所有权利。
A new drug delivery formulation, biodegradable glycolic acid-lactic acid copolymer (PGLA) microspheres incorporating cisplatin (CDDP-MS) has been developed for the treatment of peritoneal carcinomatosis. Scanning electron microscopy showed that CDDP-MS has a smooth surface and few cisplatin crystals in the hollow. An electron probe micro analyzer revealed that cisplatin was located mainly in the matrix in the state of a molecule. Release profile in vitro of CDDP from microspheres showed that the initial burst was 21.2% and the remaining CDDP was released slowly thenceforth over 14 days. Hydrolysis of CDDP-MS progresses very slowly during the 14 days, but there was no morphological change in the SEM views. The dimethylformamide content entrapped within CDDP-MS, determined by a gas chromatography, was 136 ppm at the evaporation temperature of 47 degreesC. The 50% lethal dose value of CDDP-MS, calculated by the Litchfield-Wilcoxon method, was reduced to 57% of the cisplatin solution. Therapeutic experiment on mice with peritoneal carcinomatosis showed that CDDP-MS did not enhance therapeutic effect as compared with the same dose dosage of a cisplatin aqueous solution but large quantities of cisplatin could be given in case of CDDP-MS owing to less toxicity. (C) 2003 Elsevier Science B.V. All rights reserved.