title: [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 degrees C in the same drug concentration. TPS-L-Carnitine was taken through endocytosis mediated by transporter.
  
  
  CONCLUSIONS
  TPS-L-Carnitine provides a good renal targeting property and lays the foundation for further studies in vivo.
authors: Department of Pharmacy, West China Hospital, Sichuan University, Chengdu 610041, China.
authors: Li
authors: L
authors: Li
authors: Di
authors: D
authors: Zhu
authors: Xun
authors: X
authors: Sun
mesh_terms: D002331:Carnitine / Q000138:chemical synthesis / Q000378:metabolism*; D002460:Cell Line; D004224:Diterpenes / Q000138:chemical synthesis / Q000378:metabolism*; D016503:Drug Delivery Systems; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D027701:Organic Cation Transport Proteins / Q000378:metabolism; D010616:Phenanthrenes / Q000138:chemical synthesis / Q000378:metabolism*; D011355:Prodrugs / Q000378:metabolism*; D000074058:Solute Carrier Family 22 Member 5; D019802:Succinic Acid / Q000138:chemical synthesis / Q000378:metabolism
chemical_list: D004224:Diterpenes; D004852:Epoxy Compounds; D027701:Organic Cation Transport Proteins; D010616:Phenanthrenes; D011355:Prodrugs; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; C001899:triptolide; D019802:Succinic Acid; D002331:Carnitine