阳离子纳米乳提高替尼泊苷口服吸收的研究  

Enhanced Oral Absorption of Teniposide Cationic Nanoemulsions

作　　者：牛宝华[1] 马莉[2] 刘泽莹[2] 王一鑫[1] 陈大为[1] 

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016 [2]中国科学院上海药物研究所,上海201203

出　　处：《中国医药工业杂志》2013年第8期781-785,共5页Chinese Journal of Pharmaceuticals

基　　金：国家重大科学研究计划项目(2009CB930304)

摘　　要：采用表面活性剂聚乙二醇1000维生素E琥珀酸酯(TPGS)、聚乙二醇十二羟基硬脂酸酯(HS-15),阳离子脂质十八胺及中链甘油三酯(MCT),以分子自组装技术制备替尼泊苷阳离子纳米乳。所得制品平均粒径为(61.9±4.5)nm,电位为(+8.38±3.34)mV。体外细胞毒性试验显示,本品能显著提高替尼泊苷对人肺癌细胞A549的杀伤作用。与替尼泊苷溶液相比,本品能显著提高替尼泊苷在小鼠肠道及心、肝、脾、肺和肾中的分布。大鼠体内药动学研究表明,本品可显著提高替尼泊苷的峰浓度及AUC,口服相对生物利用度是溶液组的380%。The teniposide cationic nanoemulsions （TCN） were prepared by a self-assembly technique with D-ct- tocopherol polyethylene glycol 1000 succinate （TPGS）, 12-hydroxystearic acid-polyethylene glycol copolymer （HS- 15）, octadeeylamine and medium chain triglyceride. The product was nanometer-sized with the mean diameter of （61.9± 4.5） nm and the ζ potential of （＋8.38±3.34）inV. The MTT assay showed that the in vitro antitumor activity of teniposide in A549 cells was significantly increased by TCN. The distributions of teniposide from TCN in the intestinal tract and tissues such as heart, liver, spleen, lung and kidney of mice were obviously enhanced compared with teniposide solution. Moreover, the results of in vivo pharmacokinetic test in rats indicated that the Cmax and AUC of teniposide from TCN were significantly enhanced. Compared with teniposide solution, the oral bioavailability of TCN was 380 %.

关 键 词：替尼泊苷 自组装 阳离子纳米乳 口服吸收 

分 类 号：R944.9[医药卫生—药剂学]