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Claudin-5-Binders Enhance Permeation of Solutes across the Blood-Brain Barrier in a Mammalian Model. | LitMetric

Claudin-5-Binders Enhance Permeation of Solutes across the Blood-Brain Barrier in a Mammalian Model.

J Pharmacol Exp Ther

Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan (Y.H., K.S., Y.O., A.W., T.D., K.Y., M.K.); Proteo-Science Center, Ehime University, Ehime, Japan (H.T., T.S.); and Life Science Research Laboratories, Wako Pure Chemical Industries, Ltd., Hyogo, Japan (K.E., M.T., Y.S.)

Published: November 2017

A current bottleneck in the development of central nervous system (CNS) drugs is the lack of drug delivery systems targeting the CNS. The intercellular space between endothelial cells of the blood-brain barrier (BBB) is sealed by complex protein-based structures called tight junctions (TJs). Claudin-5 (CLDN-5), a tetra-transmembrane protein is a key component of the TJ seal that prevents the paracellular diffusion of drugs into the CNS. In the present study, to investigate whether CLDN-5 binders can be used for delivery of drugs to the CNS, we generated monoclonal antibodies (mAbs) specific to the extracellular domains of CLDN-5. In an in vitro model of the BBB, the anti-CLDN-5 mAbs attenuated trans-epithelial/endothelial electrical resistance and enhanced solute permeation. These anti-CLDN-5 mAbs are potential leads for the development of novel drug delivery systems targeting the CNS.

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Source
http://dx.doi.org/10.1124/jpet.117.243014DOI Listing

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