期刊
BIOMACROMOLECULES
卷 10, 期 3, 页码 505-516出版社
AMER CHEMICAL SOC
DOI: 10.1021/bm801026k
关键词
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资金
- Wallace H. Coulter Foundation
- National Institute of Health
This study describes novel quaternary ammonium beta-cyclodextrin (QA beta CD) nanoparticles as drug delivery carriers for doxorubicin (DOX), a hydrophobic anticancer drug, across the blood-brain barrier (BBB). QA beta CD nanoparticles show 65-88 nm hydrodynamic radii with controllable cationic properties by adjusting the incorporated amount of quaternary ammonium group in their structure. ATR-FTIR studies confirm the complexation between the QA beta CD nanoparticles and DOX QA beta CD nanoparticles are not toxic to bovine brain microvessel endothelial cells (BBMVECs) at concentrations up to 500 mu g.mL(-1). They also do not change the integrity of BBMVEC monolayers, an in vitro BBB model, including transendothelial electrical resistance value, Lucifer yellow permeability, tight junction protein occludin and ZO-1 expression and morphology, cholesterol extraction, and P-glycoprotein (P-gp) expression and efflux activity, at a concentration of 100 mu g.mL(-1). Some QA beta CD nanoparticles not only are twice as permeable as dextran (M-w = 4000 g.mol(-1)) control, but also enhance DOX permeability across BBMVEC monolayers by 2.2 times. Confocal microscopy and flow cytometry measurements imply that the permeability of QA beta CD nanoparticles across the in vitro BBB is probably due to endocytosis. DOX/QA beta CD complexes kill U87 cells as effectively as DOX alone. However, QA beta CD nanoparticles completely protect BBMVECs from cytotoxicity of DOX at 5 and 10 mu M after 4 h incubation. The developed QA beta CD nanoparticles have great potential in safely and effectively delivering DOX and other therapeutic agents across the BBB.
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