Modulation of the tight junction (TJ) seal is a promising option for increasing the transdermal absorption of drugs. The binding of the claudin (CLDN) family of tetra-transmembrane proteins through cis- and trans-interactions is an integral part of seal formation. Because epidermal TJs contain CLDN-1 and -4, a binder for these CLDNs may be a useful modulator of the permeability of the epidermal barrier. The present study investigated whether m19, which can bind to CLDN-1/-4, modulates the integrity of epidermal TJs and the permeability of cell sheets to solutes. Treatment of normal human epidermal keratinocytes (NHEKs) with m19 reduced the integrity of TJs. A CLDN-1–specific binder (7A5) also weakened the TJ seal in NHEKs. Treatment of NHEKs with 7A5 enhanced permeation of a paracellular permeation marker. These findings indicate that CLDN-1 is a potential target for modulating the permeability of the epidermis and that 7A5 is a promising candidate molecule for development as a dermal absorption enhancer.
See article at J Pharmacol Exp Ther 2015, 354:440–447.
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