Nishioka Y, Kyotani S, Okamura M, Miyazaki M, Okazaki K, Ohnishi S, Yamamoto Y, Ito K
Department of Pharmacy, Kochi Medical School Hospital, Japan.
Chem Pharm Bull (Tokyo). 1990 Oct;38(10):2871-3. doi: 10.1248/cpb.38.2871.
To increase cisplatin (CDDP) content, to suppress burst effect during the initial phase of drug release, and to improve the capacity of the system for sustained release, we prepared various types of CDDP chitosan microspheres incorporating chitin and investigated the content of CDDP and its in vitro release kinetics from these microspheres. The results of this study showed that the CDDP content increased with increasing chitosan concentration and that the incorporation of chitin in the carrier matrix produced a more pronounced increase in drug content. The addition of chitin also led to inhibition of the initial burst effect. The rate of CDDP release reduced with increasing concentration of chitosan: that is, the 50% CDDP release time was about 0.5 h with the microspheres prepared with 1.0% of chitosan and about 4.5 h with those prepared with 5.0% of chitosan, indicating about nine-fold prolongation. The addition of chitin further resulted in retardation of the rate of CDDP release. Meanwhile, our chitosan microspheres were shown to undergo enzymatic degradation by lysozymes.
为了提高顺铂（CDDP）含量，抑制药物释放初始阶段的突释效应，并提高体系的缓释能力，我们制备了多种包含甲壳素的CDDP壳聚糖微球，并研究了这些微球中CDDP的含量及其体外释放动力学。本研究结果表明，CDDP含量随壳聚糖浓度的增加而增加，且在载体基质中加入甲壳素使药物含量有更显著的增加。甲壳素的添加还导致了初始突释效应的抑制。CDDP释放速率随壳聚糖浓度的增加而降低：即，用1.0%壳聚糖制备的微球，50%CDDP释放时间约为0.5小时，而用5.0%壳聚糖制备的微球，该时间约为4.5小时，表明延长了约9倍。甲壳素的添加进一步导致CDDP释放速率减慢。同时，我们的壳聚糖微球显示可被溶菌酶进行酶解降解。
