Journal
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 42, Issue 1-2, Pages 148-155Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejps.2010.11.005
Keywords
Blood-brain barrier; Murine brain microvascular endothelial cell; Co-culture
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Funding
- New York State Office for Science, Technology, and Academic Research (NYSTAR)
- National Science Foundation through the Nanobiotechnology Center (NBTC)
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In vitro blood-brain barrier (BBB) models help predict brain uptake of potential central nervous system drug candidates. Current in vitro models are composed of brain microvascular endothelial cells (BMEC) that are isolated from rat, bovine, or porcine. However, most in vivo studies on drug transport through the BBB are performed in small laboratory animals, specially mouse and thus murine in vitro BBB models serve as better surrogates to correlate with these studies. Here we describe the functional characterization of a reproducible in vitro model composed of murine BMEC co-cultured with rat primary astrocytes in the presence of biochemical inducing agents. The co-cultures presented high TEER and low sodium fluorescein permeability. Expression of specific BBB tight junction proteins (occludin, claudin-5, ZO-1) and the functionality of transporters (Pgp, GLUT1) were detected by immunocytochemistry and Western blotting. These results indicated a 2.5-fold increase in the expression levels of these proteins in the presence of astrocytes. In addition, a high correlation coefficient (0.98) was obtained between the permeability of a series of hydrophobic and hydrophilic drugs and their corresponding in vivo values. These results together establish the utility of this murine model for future drug transport, pathological, and pharmacological characterizations of the BBB. (C) 2010 Elsevier B.V. All rights reserved.
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