TPGS修饰的青蒿琥酯脂质体及其代谢产物在大鼠体内组织分布研究

Tissue distribution of TPGS modified artesunate liposome and its metabolites in rats

青蒿琥酯作为一种抗疟药物被广泛使用,制成脂质体可以改变其生物利用度差的特点,同时其在体内的组织分布可能改变,因此需对TPGS修饰的青蒿琥酯脂质体（ARS-TPGS-Lipo）在大鼠体内的组织分布进行研究。采用薄膜水化法制备ARS-TPGS-Lipo和青蒿琥酯脂质体（ARS-Lipo）,同时建立LC-MS/MS检测大鼠组织中青蒿琥酯（ARS）和双氢青蒿素（DHA）含量的方法,并测定大鼠尾静脉注射ARS-TPGS-Lipo,ARS-Lipo和ARS注射液（5 mg·kg^-1）后不同时间点的组织药物浓度。实验结果显示该方法适用于分析生物样品中的ARS和DHA的含量。ARS-TPGS-Lipo,ARS-Lipo和ARS组中的ARS及其代谢产物DHA在大鼠的组织中分布差异较大,使用TPGS修饰后的青蒿琥酯脂质体中的药物浓度在肝脏中浓度最高,且有显著性差异。ARS经注射给药后1 h内快速消除;ARS-Lipo组测得的ARS和DHA在肝、脾中的浓度较高;而ARS-TPGS-Lipo组中测得的ARS和DHA仅在肝脏中的浓度显著提高（P〈0.05）。

Artesunate,which is a widely used anti-malaria medicine,can be made into liposome to overcome its poor bioactivity.Its tissue distribution in rats may change with different dosage forms,which therefore shall be studied after ARS-TPGS-Lipo was injected. Based on this experiment,ARS-TPGS-Lipo and ARS-Lipo were prepared by thin-film hydration method. LC-MS/MS method was used to simultaneously determine ARS and DHA in rat tissues at different time points. The results showed that this method was suitable for the content analysis of ARS and DHA in biological samples. The distribution of ARS and DHA in ARS-TPGS-Lipo,ARS-Lipo and ARS groups were quite different. The content of ARS-TPGS-Lipo in liver was the highest,with significant differences. ARS and DHA contents in ARS group eliminated rapidly. ARS and DHA contents in ARS-Lipo group were higher in liver and spleen,while those in ARS-TPGS-Lipo group significantly increased only in liver（ P〈0. 05）.