地塞米松当归多糖前体药在大鼠体内的结肠靶向释药研究

Colon-targeted delivery system of dexamethasone-angelica sinensis polysaccharides prodrug in rats

目的:探讨以当归多糖为载体的地塞米松前体药在大鼠胃肠道内的转运及活性药物的释放情况。方法:地塞米松及其当归多糖前体药按1.96mg·kg-1(以地塞米松量计)给大鼠灌胃,采用高效液相色谱法检测地塞米松在大鼠胃肠道不同部位的分布及血药浓度变化。结果:地塞米松当归多糖前体药灌胃后,释放出的地塞米松只分布在盲肠和结肠的内容物及粘膜中,在胃和小肠的内容物及粘膜中未检测到地塞米松释放;释放出的地塞米松吸收缓慢,达峰时间(tmax)为7.2h,血浆药物峰浓度(Cmax)为42μg·L-1,曲线下面积(AUC)为334μg·h·L-1。地塞米松灌胃后,药物主要分布在胃、小肠近端及小肠远端的内容物和粘膜中,药物吸收迅速,tmax为2.2h,Cmax为2120μg·L-1,AUC为11875μg·h·L-1。结论:以当归多糖为载体的地塞米松前体药具有良好的结肠定位转释作用,有可能成为一种具有良好应用前景的结肠炎治疗药物。

AIM： To explore the transport and delivery of active drug from dexamethasone-angelica sinensis polysaccharides prodmg in the gastrointestinal tract of rats. METHODS： Dexamethasone and the prodrug were orally administered to rats at the dose of 1.96 mg· kg^-1（calculated by carried dexamethasone）. The drugs in the plasma and contents of different parts of the rats＇ gastrointestinal tract were determined by high performance liquid chromatography （ HPLC ）. RESULTS： Dexamethasone carried by the prodrug was mainly released in the contents and mucosa of cecum and colon after oral administration of the prodrug. The absorption of released dexamethasone was reduced significantly. The peak time, peak concentration and AUC were 7.2 h , 42 μg2L^-1 and 334μg· h· L^- 1, respectively. However, free dexamethasone was found mainly in the contents and mucosa of the stomach, proximal and distal small intestine after oral administration. The peak time, peak concentration and AUC were 2.2 h, 2 120 μg·L^-1 and 11 875 μg·h·L^-1, respectively. CONCLUSION： Dexamethasone can be specifically delivered to the cecum and colon by using dexamethasone- angelica sinensis polysaccharides prodrug. The absorption of dexamethasone was reduced significantly and the drug concentration in colon was increased significantly. The prodrug has a potential in the treatment of colitis.