期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 98, 期 10, 页码 3748-3760出版社
ELSEVIER SCIENCE INC
DOI: 10.1002/jps.21669
关键词
dendrimers; blood-brain barrier; permeability; nanotechnology; in vitro models
资金
- Natural Sciences and Engineering Research Council of Canada
Dendrimers have emerged as a promising drug delivery system due to their well defined size, tailorability, and multifunctional nature. However, their application in brain delivery is relatively a new area of research. The present study was aimed at evaluating the uptake and permeation of polyether-copolyester (PEPE) dendrimers across the blood-brain barrier model and exploring the underlying mechanisms. Saturation was observed in the uptake of rhodamine B labeled PEPE dendrimers by brain vascular endothelial (bEnd.3) cells at high concentrations. Clathrin and caveolin inhibitors produced partial inhibition of the dendrimer uptake, signifying contribution of both pathways in the uptake process. PEPE dendrimers were able to cross in vitro BBB model in high amounts with P-app of 19.7 +/- 1.9 x 10(-6) cm/s and 38.6 +/- 4.1 x 10(-6) cm/s for den-1-(G2)-400 and den-2-(G2)-400, respectively; and only 11-14% reduction in transendothelial electrical resistance during initial 4 h. The results of this study suggest that architecture of dendrimers plays a major role not only in influencing the extent and mechanism of uptake by bEnd.3 cells but also permeation across the BBB model. (C) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3748-3760, 2009
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