去甲基斑蝥素纳米粒肠道吸收的体内外相关性研究  

Intenstinal absorption mechanism and in vitro-in vivo correlation of norcantharidin nanoparticles

作　　者：陈晓艳[1] 刘扬[1] 张玮[1] 贝永燕[1] 许静玉[1] 王文娟[1] 张学农[1,2] 

机构地区：[1]苏州大学药学院,江苏苏州215123 [2]苏州利元医药科技有限公司,江苏苏州215022

出　　处：《中草药》2009年第12期1930-1935,共6页Chinese Traditional and Herbal Drugs

基　　金：国家科技支撑计划课题资助(2006BAI09B00);国家科技部科技型中小企业技术创新基金(07C26223201333);江苏省"六大人才高峰"资助项目;江苏省卫生厅招标项目(H200630);国家大学生创新基金(57315924)

摘　　要：目的考察去甲基斑蝥素壳聚糖纳米粒(NCTD-CS-NP)的体外释放以及其在体、离体肠吸收特征,并建立三者之间的相关性。方法采用离子诱导交联法制备NCTD-CS-NP,动态透析法考察其体外释药动力学;以去甲基斑蝥素(NCTD)水溶液为对照,采用大鼠离体外翻肠法与在体回流法研究纳米粒制剂在大鼠小肠区段内的吸收规律;并对体外释放、离体及在体肠吸收进行相关性研究。结果NCTD与NCTD-CS-NP在大鼠小肠部位的吸收速率常数(K_a)依次为:十二指肠>空肠>回肠>结肠;两种剂型在十二指肠的K_a分别为15.69、29.16 h^(-1),纳米粒制剂的吸收显著好于水溶液;同一剂型,不同质量浓度药物的大鼠小肠部位的吸收速率之间无显著影响(P>0.05),均符合一级吸收动力学过程;离体小肠外翻吸收的趋势与在体吸收一致,仅K_a稍有降低,二者呈现良好的相关性(r=0.999 4)。结论壳聚糖纳米粒有利于药物释放,可有效促进NCTD在肠黏膜的吸收;NCTD在肠道中上部吸收明显,药物质量浓度对吸收速率无显著影响;NCTD体外释药、在体、离体肠吸收三者之间相关性良好。Objective To study the accumulative release of norcantharidin chitosan nanoparticles （NCTD-CS NP） in vitro, investigate its properties and absorption characters in rat intestine in vivo and in vitro, and evaluate the correlation among the release in vitro, the absorption in rat intestine in vivo and in vitro. Methods NCTD-CS NP was prepared by ionic cross-linkage process, dynamic dialysis was used to study the release dynamics of NCTD-CS NP in vitro. The intestine in rats was cannulated for in vivo reeirculation and everted gut sac in vitro. The absorption character and regularity were studied at various intestine segments and at different concentration. Results The absorption rate constants （Ka） of NCTD and NCTD-CS-NP in various segments were duodenum ） jejunum 〉 ileum 〉 colon. At the duodenum, the Ka of NCTD and NCTD CS-NP were 15.69 and 29.16 h 1 , respectively. The concentration had no distinctive effect on the absorption kinetics （P 〉 0.05）. The absorption of NCTD was a first order process with passive diffusion mechanism. The absorption law in vivo was the same as in vitro, the correlation coefficient between them was 0. 999 4. Conclusion NCTD-CS-NP could improve the absorption of NCTD in rat small intestine. NCTD is well absorbed at the superior and middle segments of intestine. The concentration of NCTD has no distinctive effect on the absorption kinetics. The release of drug in vitro and its up-take is well correlated.

关 键 词：去甲基斑蝥素 纳米粒 药物累积释放 吸收动力学 

分 类 号：R285.61[医药卫生—中药学]