title: Design, synthesis and biological evaluation for docetaxel-loaded brain targeting liposome with "lock-in" function.
abstract: BACKGROUND
  Glucose-modified liposome showed a good brain-targeting ability. However, bidirectional transport of glucose transporter-1 (GLUT1) might reversely pump drugs out of the brain before releasing from the liposomes.
  
  
  OBJECTIVE
  To overcome the bidirectional delivery of GLUT1, the thiamine disulfide system (TDS), with ability of "lock-in", was introduced and a new ligand, L-TDS-G, was designed and synthesized.
  
  
  METHODS
  The liposome was prepared and characterized for particle size, zeta potential, surface morphological property, encapsulation efficiency and release profile. C6 glioma cells were used as an in vitro model to access the cellular uptake abilities and cytotoxicity of the liposomes. Competition assay was performed to validate the GLUT1-mediated transport mechanism. Furthermore, the brain targeting abilities of the liposomes were evaluated through in vivo.
  
  
  RESULTS
  The preliminary evaluation in vivo demonstrated that L-TDS-G-coated liposome has an improved targeting ability and significantly increased the area under the concentration-time of docetaxel in brain as compared to naked docetaxel, non-coated and L-G coated liposomes. The relative uptake efficiency and concentration efficiency were enhanced by 3.82- and 4.99-fold compared to that of naked docetaxel, respectively.
  
  
  CONCLUSIONS
  The results of this study indicated that L-TDS-G-coated liposome is a promising drug delivery system to enhance the brain concentrations of chemotherapeutic agents.
authors: a Key Laboratory of Drug Targeting of Education Ministry, West China School of Pharmacy, Sichuan University Chengdu P.R. China.
authors: Xiaocen
authors: X
authors: Li
authors: a Key Laboratory of Drug Targeting of Education Ministry, West China School of Pharmacy, Sichuan University Chengdu P.R. China.
authors: Boyi
authors: B
authors: Qu
authors: a Key Laboratory of Drug Targeting of Education Ministry, West China School of Pharmacy, Sichuan University Chengdu P.R. China.
authors: Xiuxiu
authors: X
authors: Jin
authors: a Key Laboratory of Drug Targeting of Education Ministry, West China School of Pharmacy, Sichuan University Chengdu P.R. China.
authors: Li
authors: L
authors: Hai
authors: a Key Laboratory of Drug Targeting of Education Ministry, West China School of Pharmacy, Sichuan University Chengdu P.R. China.
authors: Yong
authors: Y
authors: Wu
keywords: Blood-brain barrier; brain targeting; competition assay; cytotoxicity; glucose; glucose transporter-1; thiamine disulfide system