title: A novel strategy for a drug delivery system using a claudin modulator.
abstract: With the continued progress in genomic drug discovery, the high-throughput production of drug candidates has become possible, and thus today there are a number of candidates that are extremely effective both in cell-free and in cell models. However, a drug delivery system suitable for the high-throughput production has yet to be fully developed. In tissues, the tight junction (TJ) plays a pivotal role as both a barrier to restrict various substances and in intra-tissue maintenance. Claudin, a ca. 23 kDa transmembrane protein with four transmembrane domains, is responsible for the TJ functions. Interestingly, for each of the 24 members of the claudin family, expression profiles and exact barrier functions differ. Therefore, claudin may be a potential target for use as a drug delivery system via a paracellular route. The C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) is known to modulate the barrier function of claudin. We found that C-CPE is a potent absorption-enhancer and that this enhancing activity is 400-fold greater than clinically used enhancers. The enhancing activity examined in this study involved an interaction between C-CPE and claudin-4. These findings indicate that claudin might be a novel target for a drug delivery system. In the current review, we describe about background and data on our research about claudin modulator, and we also discuss the possibility of the use of the claudin family in a new approach for developing a drug delivery system.
authors.affiliation: Department of Bio-Functional Molecular Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan. masuo@phs.osaka-u.ac.jp
authors.forename: Masuo
authors.initials: M
authors.lastname: Kondoh
authors.forename: Azusa
authors.initials: A
authors.lastname: Takahashi
authors.forename: Makiko
authors.initials: M
authors.lastname: Fujii
authors.forename: Kiyohito
authors.initials: K
authors.lastname: Yagi
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D062506:Claudin-4; D016503:Drug Delivery Systems / Q000379:methods*; D004768:Enterotoxins / Q000494:pharmacology*; D006801:Humans; D007408:Intestinal Absorption; D008565:Membrane Proteins / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D019108:Tight Junctions / Q000187:drug effects
chemical_list: C568157:CLDN4 protein, human; D062506:Claudin-4; D004768:Enterotoxins; D008565:Membrane Proteins; D010446:Peptide Fragments; C035598:enterotoxin, Clostridium