a Experiment Center for Science and Technology , Shanghai University of Traditional Chinese Medicine , Shanghai , China.
b Department of Chemistry , College of Pharmacy, Shanghai University of Traditional Chinese Medicine , Shanghai , China.
Drug Dev Ind Pharm. 2018 Sep;44(9):1528-1535. doi: 10.1080/03639045.2018.1483383. Epub 2018 Jun 21.
The objective of this study (ARS-TPGS-Lipo) was to enhance the stability, encapsulation efficiency (EE), improve AUC, circulation time and liver targeting of ARS-TPGS-Lipo.
ARS-TPGS-Lipo was prepared by thin-film dispersion method and characterized by TEM. The EE, in vitro release and stability of ARS-TPGS-Lipo were detected by HPLC and UV. In addition to the safety evaluation, the pharmacokinetics and tissue distribution studies were also carried out after i.v. administration.
The size, PDI, zeta potential, and EE of ARS-TPGS-Lipo were 126.7 ± 9.9 nm, 0.182 ± 0.016, -10.1 ± 1.43 mV, and 78.8 ± 1.89%, respectively. ARS-TPGS-Lipo showed the slow-release effect in vitro release experiments. The AUC of ARS in the ARS-TPGS-Lipo group was 7.51 times higher than in the ARS group after i.v. administration and the circulation time was significantly prolonged. The tissue distribution results showed the components of artesunate and its metabolism DHA of the ARS-TPGS-Lipo group were much higher in liver than the ARS-Lipo group.
ARS-TPGS-Lipo was prepared successfully, which had the smaller vesicles size with a better PDI, better stability, higher EE, and slow-release. The results of safety evaluation indicated that ARS-TPGS-Lipo had no hematotoxicity and hepatorenal toxicity. The pharmacokinetic studies indicated ARS-TPGS-Lipo had higher AUC, longer circulation time and better liver targeting.
本研究（ARS-TPGS-Lipo）旨在提高 ARS-TPGS-Lipo 的稳定性、包封效率（EE）、增加 AUC、延长循环时间并实现肝靶向。
采用薄膜分散法制备 ARS-TPGS-Lipo，通过 TEM 进行表征。采用 HPLC 和 UV 检测 ARS-TPGS-Lipo 的 EE、体外释放和稳定性。除了安全性评价外，还进行了静脉给药后的药代动力学和组织分布研究。
ARS-TPGS-Lipo 的粒径、PDI、Zeta 电位和 EE 分别为 126.7±9.9nm、0.182±0.016、-10.1±1.43mV 和 78.8±1.89%。ARS-TPGS-Lipo 在体外释放实验中表现出缓慢释放的效果。静脉注射后，ARS-TPGS-Lipo 组的 ARS AUC 是 ARS 组的 7.51 倍，循环时间明显延长。组织分布结果表明，ARS-TPGS-Lipo 组的青蒿琥酯及其代谢物 DHA 成分在肝脏中的含量明显高于 ARS-Lipo 组。
成功制备了 ARS-TPGS-Lipo，其具有更小的囊泡粒径、更好的 PDI、更好的稳定性、更高的 EE 和缓慢释放的特点。安全性评价结果表明，ARS-TPGS-Lipo 无血液毒性和肝肾毒性。药代动力学研究表明，ARS-TPGS-Lipo 具有更高的 AUC、更长的循环时间和更好的肝靶向性。
