Claudin-5-Binders Enhance Permeation of Solutes across the Blood-Brain Barrier in a Mammalian Model.
J Pharmacol Exp Ther
; 363(2): 275-283, 2017 11.
Article
em En
| MEDLINE
| ID: mdl-28819070
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Barreira Hematoencefálica
/
Claudina-5
Limite:
Animals
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Female
/
Humans
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Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article