Cellular Uptake of TPS-L-Carnitine Synthesised as Transporter-based Renal Targeting Prodrug

【Abstract】 Objective To synthesize transporter-based renal targeting prodrug TPS-L-Carnitine 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 ℃ 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.