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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rn(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法检测大鼠组织中artesunate(ARS)和dihydro-artemisinin(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(5mg/kg)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1h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 is widely used as an anti-malarial drug. Liposomes can change the bioavailability of artesunate and its tissue distribution in the body may change. Therefore, artesunate ester modified by TPGS Plastid r n (ARS-TPGS-Lipo) tissue distribution in rats was studied. The ARS-TPGS-Lipo and artesunate liposomes (ARS-Lipo) were prepared by the membrane hydration method. Meanwhile, the contents of artesunate (ARS) and dihydro-artemisinin . The concentrations of TUNEL at different time points after the tail vein injection of ARS-TPGS-Lipo, ARS-Lipo and ARS injection (5mg / kg) were determined. The experimental results show that this method is suitable for the analysis of ARS and DHA content in biological samples. ARS-TPGS-Lipo, ARS-Lipo and ARS groups of ARS and its metabolite DHA distribution in rat tissue differences, the use of TPGS modified artesunate liposome drug concentration in the liver The highest concentration, and there are significant differences. ARS was rapidly eliminated within 1 h after injection; the concentrations of ARS and DHA in the liver and spleen in the ARS-Lipo group were higher; while the ARS and DHA in the ARS-TPGS-Lipo group were only found in the liver Concentration significantly increased (P <0.05).