Objective To study the effect of dual-mediated brain targeting liposomes(RVGPR9-SSL)as delivery vehicles on the blood brain barrier(BBB)permeability of doxorubicin(DOX),providing a new strategy for brain drug delivery.Methods The dual-mediated brain targeting liposomes(RVGPR9-SSL)were prepared by thin film dispersion/leading compound method.And the chemo-therapeutic drug DOX was encapsulated in RVGPR9-SSL(DOX@RVGPR9-SSL).Brain microvascular endothelial cells(BMVEC)were cultured and used to construct in vitro BBB models.The BBB model was then evaluated by a 4h leakage test,transmembrane resist-ance value(TEER)measurement,and tight junctions between cells observed by scanning transmission electron microscope(SEM).After the successful construction of the BBB model,the integrity of RVGPR9-SSL after crossing the BBB was investigated by confocal laser scanning microscopy using fluorescence a resonance energy transfer(FRET)pair.The effect of RVGPR9-SSL administration on BBB in-tegrity was evaluated by comparative analysis of BBB morphology and TEER values before and after liposome administration.The BBB per-meability of DOX@RVGPR9-SSL was investigated by fluorescence spectrophotometry.Results The encapsulation efficiency of DOX@RVGPR9-SSL was 97.25％.The TEER values of the constructed BBB model were all greater than 200Ω·cm2,and it was observed by SEM that the BMVEC cells were closely arranged and there were obvious tight junctions,indicating that the in vitro BBB model was suc-cessfully established and could be used for the investigation of BBB permeability.The 4h BBB cumulative permeability of DOX@RVGPR9-SSL was greater than 10％,which was significantly higher than that of free DOX.And both BBB and liposomes maintained good integrity after administration.Conclusion RVGPR9-SSL can significantly improve the BBB permeability of DOX,indicating that it is a very promising brain drug delivery vehicle.
Dual-mediated brain targeting liposomesBlood brain barrier(BBB)Cumulative permeabilityFluorescence reso-nance energy transfer(FRET)
万方数据
维普
