title: Synthesis and evaluation of a novel lipophilic folate receptor targeting ligand.
abstract: BACKGROUND
  Folate receptor (FR)-targeted liposomes have been investigated as delivery vehicles for anticancer drugs. A novel lipophilic FR ligand, folate-glutathione-polyethyleneglycol-distearoyl phosphatidylethanolamine (F-GSH-PEG-DSPE), was synthesized, incorporated into liposomes and evaluated for FR targeting efficiency. These liposomes were then evaluated as carriers of the chemotherapy agent vincristine (VIN).
  
  
  METHODS
  F-GSH-PEG-DSPE was synthesized and FR-targeted liposomes loaded with either calcein (F-L-Calcein) or VIN (F-L-VIN) were prepared by thin film hydration followed by polycarbonate membrane extrusion and, in the case of VIN, by remote loading. To assess liposome stability, the uptake of F-L-VIN in KB (FR+) cancer cells was measured after storage under 4°C for 3 months. Comparative pharmacokinetic studies were carried out with F-L-VIN and L-VIN (non-targeted control liposomes).
  
  
  RESULTS
  F-L-Calcein showed significantly higher cellular uptake in KB cells compared to non-targeted liposomes. In addition, F-L-VIN showed enhanced cytotoxicity in KB cells in vitro compared to control liposomes. Pharmacokinetic parameters indicated that both F-L-VIN and control liposomes had higher area under the curve (AUC), mean residence time (MRT), elimination half life (t1/2-β) and lower total body clearance (CL) than those of free VIN, while there were no significant differences between these liposomal formulations.
  
  
  CONCLUSIONS
  F-GSH-PEG-DSPE is effective as a novel ligand for the synthesis of FR-targeted liposomes.
authors: Department of Pharmacy, Wuhan University, China.
authors: Ying
authors: Y
authors: Liu
authors: Songlin
authors: S
authors: Xu
authors: Lesheng
authors: L
authors: Teng
authors: Bryant
authors: B
authors: Yung
authors: Jing
authors: J
authors: Zhu
authors: Hong
authors: H
authors: Ding
authors: Robert J
authors: RJ
authors: Lee