四川大学学报（医学版）2012，Vol.43Issue(6)：936-940,5.
转运体介导的肾靶向雷公藤内酯醇前体药物TPS-L-Carnitine的合成及体外细胞摄取研究
Cellular Uptake of TPS-L-Carnitine Synthesised as Transporter-based Renal Targeting Prodrug
李里 1朱迪 2孙逊2
作者信息
- 1. 四川大学华西医院 药剂科,成都 610041
- 2. 四川大学华西药学院,成都 610041
- 折叠
摘要
Abstract
Objective To synthesize transporter-based renal targeting prodrug TPS-L-Camitine and to determine its cellular uptake in vitro. Methods Triptolide (TP) was conjugated with L-carnitine using succinate as the linker to form TPS-L-Carnitine, which could be specifically recognized by OCTN2, a cationic transporter with high affinity to L-Carnitine and is highly expressed on the apical membrane of renal proximal tubule cells. Cellular uptake assays of the prodrug and its parent drug were performed on HK-2 cells, a human proximal tubule cell line, in different temperature, concentration and in the presence of competitive inhibitors. Results TPS-L-Carnitine was taken up into HK-2 cells in a saturable and temperature- and concentration-dependent manner. The uptake process could be inhibited by the competitive inhibitors. The uptake of TPS-L-Carnitine was significantly higher than that of TP at 37 °C in the same drug concentration. TPS-L-Carnitine was taken through endocytosis mediated by transporter. Conclusion TPS-L-Carnitine provides a good renal targeting property and lays the foundation for further studies in vivo.关键词
肾靶向/肾靶向前体药物/雷公藤内酯醇/雷公藤内酯醇丁二酸酯-L-肉毒碱Key words
Renal targeting/Renal targeting prodrug/Triptolide/TPS-L-Carnitine引用本文复制引用
李里,朱迪,孙逊..转运体介导的肾靶向雷公藤内酯醇前体药物TPS-L-Carnitine的合成及体外细胞摄取研究[J].四川大学学报（医学版）,2012,43(6):936-940,5.
