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, 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 specific to the extracellular domains of CLDN-5. In an in vitro model of the blood-brain barrier, the anti-CLDN-5 mAbs dose-dependently attenuated TEER and enhanced solute permeation. These anti-CLDN-5 monoclonal antibodies are potential leads for the development of novel drug delivery systems targeting the CNS.
- The American Society for Pharmacology and Experimental Therapeutics