[Claudin as a novel target for drug delivery system].
Recent remarkable progress in genomic novel drug discovery enables us to prepare drug candidates with tremendous diversity in a high-throughput-manner. In clinical use of these candidates, they should be effectively delivered to a target-tissue in body. But delivery systems suitable for the high-throughput discovery of drugs have never been established. Tight junctions (TJs) play a pivotal role in compartmentation of each tissues and maintenance of their intra-circumstances. Claudin, a membrane protein with four trans-membrane domains, have recently found to be responsible for the barrier-function of TJs. Claudin is constituted of 24 family members, and expression profiles and barrier-function of claudin differ interestingly among the family members. These findings indicate that a modulator of the unique barrier-function of claudin may be used for drug delivery. In this respect, we have investigated whether a claudin is a target for drug delivery. A claudin modulator (C-terminal fragment of Clostridium perfringens enterotoxin, C-CPE) had 400-fold jejunal absorption-enhancing activity to a clinically used absorption-enhancer, and interaction between C-CPE and claudin was essential for the enhancing activity. We have already prepared a screening system for claudin-targeting molecule. Now we are performing functional domain mapping of C-CPE, and we will attempt to prepare a various type of claudin modulator in a future. In the current review, I introduce our recent works on development of a novel strategy for drug delivery system using claudin modulator, and I discuss also possibility of claudin modulator in drug delivery system.
Kondoh
Masuo
M
Department of Bio-Functional Molecular Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, Suita City, Japan. masuo@phs.osaka-u.ac.jp
D000818:Animals; D002451:Cell Compartmentation; D062465:Claudin-3; D062506:Claudin-4; D057167:Claudins; D016503:Drug Delivery Systems; D015195:Drug Design; D004768:Enterotoxins; D006801:Humans; D008565:Membrane Proteins; D019108:Tight Junctions / Q000502:physiology
C568122:CLDN3 protein, human; C568157:CLDN4 protein, human; D062465:Claudin-3; D062506:Claudin-4; D057167:Claudins; D004768:Enterotoxins; D008565:Membrane Proteins; C035598:enterotoxin, Clostridium; C502011:claudin 8; C122101:claudin 6