伊立替康PEO-PPO-PEO胶束的制备和表征及其降低药物消化道毒性的机制研究  

Preparation and characterization of irinotecan hydrochloride loaded PEO-PPO-PEO micelles and its mechanism of decreasing drug intestinal toxicity

作　　者：张馨欣[1] 郭仕艳[1] 李菲菲[1] 甘勇[1] 

机构地区：[1]中国科学院上海药物研究所,上海201203

出　　处：《药学学报》2012年第11期1534-1540,共7页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(30901865);河北省自然科学基金资助项目(C2011319010)

摘　　要：本文以具有乳腺癌耐药蛋白(BCRP)抑制作用的高分子嵌段共聚物PEO20-PPO70-PEO20为载体材料,制备了包载伊立替康的PEO-PPO-PEO胶束,并研究其降低药物迟发性腹泻和肠黏膜损伤的机制。采用高表达转运蛋白BCRP的细胞株MDCKII/BCRP为模型,在体外考察了高分子材料PEO20-PPO70-PEO20及其制备的胶束对伊立替康跨膜转运的影响,并在大鼠体内研究了PEO-PPO-PEO胶束对伊立替康经胆汁排泄、腹泻及肠黏膜损伤的作用。结果表明,PEO-PPO-PEO胶束可通过抑制BCRP介导的药物外排,从而减少伊立替康经胆汁的排泄量,改善药物引发的迟发性腹泻和肠黏膜损伤,有望成为降低喜树碱类药物消化道毒性的理想载体。In this work, we developed PEO-PPO-PEO micelles loaded with irinotecan hydrochloride （CPT-11） using breast cancer resistance protein （BCRP） inhibitory material PEO20-PPOTo-PEO20, and studied its mechanism of decreasing CPT-11 induced delayed diarrhea and intestinal toxicity. BCRP-overexpressing MDCKII （MDCKII/BCRP） cells were used to evaluate the effect of PEO20-PPO70-PEO20 and PEO-PPO-PEO micelles on transmembrane transport of CPT-11 in vitro. The biliary excretion, delayed diarrhea and intestinal damage of CPT-11 loaded PEO-PPO-PEO micelles of rats were investigated. The results showed that the obtained micelles could decrease the biliary excretion of CPT-11, ameliorate delayed diarrhea and intestinal toxicity of rats through inhibiting BCRP-mediated CPT-11 efflux. PEO-PPO-PEO micelles were promising carders to reduce intestinal toxicity of CPTs.

关 键 词：伊立替康 胶束 乳腺癌耐药蛋白 PEO—PPO-PEO 腹泻 

分 类 号：R943[医药卫生—药剂学]