Abstract
The blood-brain barrier （BBB） is a major obstacle to the delivery of drugs to the central nervous system. In the BBB, the spaces between adjacent brain microvascular endothelial cells are sealed by multiprotein complexes known as tight junctions （TJs）. Claudin-5 （CLDN-5） is the essential protein for TJ in the BBB, which restricts the influx of small molecules up to approximately 800 Da. Thus, among the many components of the TJs, CLDN-5 has received the most attention as a target for drug delivery to the brain by loosening the TJ seal. Many researchers have attempted to develop technologies to selectively inhibit the CLDN-5 and open TJ in the BBB. In this review, we introduce the use of CLDN-5 binders have been shown to enhance the permeation of small molecules from the blood into the brain without apparent adverse effects and the safety concerns of CLDN-5-targeted technologies with respect to their clinical application.
