期刊
ACTA PHARMACEUTICA SINICA B
卷 8, 期 2, 页码 261-271出版社
INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
DOI: 10.1016/j.apsb.2018.01.004
关键词
Liposomes; Disks; Intact form; BBB; BBTB; FRET
资金
- China Postdoctoral Science Foundation [2017M611464]
- National Basic Research Program of China (973 Program) [2013CB932500]
- National Natural Science Foundation of China [81773657, 81690263, 81473149]
- Shanghai Education Commission Major Project [2017-01-07-00-07E00052]
- Shanghai International Science and Technology Cooperation Project [16430723800]
The blood brain barrier (BBB) and the blood brain tumor barrier (BBTB) prevent drug and nano-drug delivery systems from entering the brain. However, ligand-mediated nano-drug delivery systems have significantly enhanced the therapeutic treatment of glioma. In this study we investigated the mechanism especially the integrity of liposomes and lipid disks while traversing the BBB and BBTB both in vitro and in vivo. Fluorophores (DiO, DiI and DiD) were loaded into liposomes and lipid disks to form Forster resonance energy transfer (FRET) nano-drug delivery systems. Using brain capillary endothelial cells as a BBB model, we show that liposomes and disks are present in the cytoplasm as their intact forms and traverse the BBB with a ratio of 0.68 parts per thousand and 1.67 parts per thousand, respectively. Using human umbilical vein endothelial cells as BBTB model, liposomes and disks remained intact and traversed the BBTB with a ratio of 2.31 parts per thousand and 8.32 parts per thousand at 3 h. Ex vivo imaging and immunohistochemical results revealed that liposomes and disks could traverse the BBB and BBTB in vivo as intact forms. In conclusion, these observations explain in part the mechanism by which nano-drug delivery systems increase the therapeutic treatment of glioma (C) 2018 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
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