Design, synthesis and biological evaluation for docetaxel-loaded brain targeting liposome with "lock-in" function

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.

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.

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.

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.

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.