Tight junction modulators: promising candidates for drug delivery.
Recent advances in genomic drug development and high-throughput technologies, such as combinatorial chemistry, high throughput screening and in silico screening, are making it easier to screen compounds with pharmaceutical activity. Drugs developed by genomic and throughput technologies traverse the epithelial and endothelial membranes. Although the paracellular pathway is a potent drug delivery route for these drugs, few strategies for their delivery have been developed because tight junctions (TJs), which exist between adjacent cells, strictly regulate the movement of solutes. Recent progress in biology of TJs has provided new insights into the biochemical and functional structure of TJs, and into the roles that occludin, claudins and tricellulin play in regulating TJ barriers. Novel strategies based on TJ-components for delivering drugs through the paracellular pathway have been developed. In this review, we discuss drug delivery through the paracellular route within the context of biology of TJs, as well as future directions of TJ-component-based drug delivery systems.
Kondoh
M
M
Department of Bio-Functional Molecular Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan. masuo@phs.osaka-u.ac.jp
Yagi
K
K
D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D062445:Claudin-1; D020650:Combinatorial Chemistry Techniques; D016503:Drug Delivery Systems; D015195:Drug Design; D023281:Genomics; D006801:Humans; D062794:MARVEL Domain Containing 2 Protein; D008565:Membrane Proteins / Q000737:chemistry; D008954:Models, Biological; D008958:Models, Molecular; D062793:Occludin; D019108:Tight Junctions / Q000187:drug effects*
C568108:CLDN1 protein, human; D062445:Claudin-1; D062794:MARVEL Domain Containing 2 Protein; C516798:MARVELD2 protein, human; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin