紫杉醇-两亲性壳聚糖胶束大鼠药代动力学和在体肠吸收  

Pharmacokinetics and in situ absorption in rat intestine of paclitaxel-loaded amphiphilic chitosan micelle

作　　者：叶青[1,2] 霍美蓉[1,2] 周建平[1,2] 

机构地区：[1]中国药科大学天然药物活性组分与药效国家重点实验室,南京210009 [2]中国药科大学药剂学教研室,南京210009

出　　处：《中国药科大学学报》2012年第5期401-405,共5页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.81102397);国家"重大新药创制"科技重大专项资助项目(No.2009ZX09310-004);天然药物活性组分与药效国家重点实验室资助项目(No.JKGQ201107)~~

摘　　要：以紫杉醇(paclitaxel,PTX)注射剂Taxol为对照,通过大鼠药代动力学及在体肠吸收实验考察N-辛基-O,N-羧甲基壳聚糖(OCC)胶束作为PTX口服给药系统的可行性。结果表明,与Taxol相比,PTX-OCC胶束经口给药在大鼠体内的cmax、AUC均显著提高(P<0.05),相对生物利用度为331.4%;PTX-OCC胶束在各个肠段吸收均显著高于Taxol(P<0.05),且十二指肠吸收略优于其他肠段,结肠、空肠和回肠吸收相近,说明OCC胶束具有显著的促吸收效果,作为难溶性药物口服递送载体具有优良的应用前景。The aim of this study was to investigate the potential feasibility of the N-octyl-O,N-carboxymethyl chitosan（OCC） micelles as oral administration carriers for paclitaxel（PTX） by pharmacokinetics and in situ absorption in rat intestine using Taxol as control.After oral administration of PTX-OCC micelles,the area under the plasma concentration-time curve（AUC） and the maximum concentration（cmax） were significantly larger than those of Taxol（P0.05）.Relative bioavailability for PTX-OCC micelles was 331.4% of that of Taxol.The absorption of PTX-OCC at different segments of intestine was significantly higher than those of Taxol（P0.05）.The apparent absorption rate（Ka） and the effective permeation coefficient（Peff） at the duodenum were a little higher than those of jejunum,ileum and colon（P0.05）.In conclusion,OCC might be a promising carrier for oral administration of poorly water-soluble drugs.

关 键 词：壳聚糖 聚合物胶束 紫杉醇 药代动力学 肠吸收 

分 类 号：R96[医药卫生—药理学]