期刊
CURRENT PHARMACEUTICAL DESIGN
卷 17, 期 25, 页码 2699-2703出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/138161211797416084
关键词
Tight junction; occludin; claudin; drug absorption
资金
- MEXT [21689006]
- Ministry of Health, Labor and Welfare of Japan
- Takeda Science Foundation
- Suzuken Memorial Foundation
- Kansai Biomedical Cluster project in Saito
- Japan Society for the Promotion of Science for Young Scientists
- Grants-in-Aid for Scientific Research [21689006] Funding Source: KAKEN
The first step in drug absorption is the passage of drug molecules across epithelial cell sheets. Epithelial cell sheets are pivotal for the maintenance of homeostasis in the body by acting as a biological barrier that separates the inside of the body from the outside environment. Intercellular space between the adjacent epithelial cells is tightly sealed by tight junctions (TJs), which prevent solutes from freely moving across the epithelial cell sheets. Modulation of the TJ barrier has been a potent strategy for drug absorption. Absorption enhancers have been investigated since the 1980s, and sodium caprate is clinically used as an absorption enhancer. However, the biochemical constituents and structures of TJs were not elucidated until 1993. Occludin, a tetra-transmembrane protein, was identified to be a structural component of TJs in 1993. Claudin, another tetra-transmembrane protein, was identified as a structural and functional component of TJs in 1998. Modulation of occludin-or claudin-barrier is novel methods to enhance drug absorption. Recently, synthetic TJ-binding peptides, a kinase of claudin and peptide fragments of toxins have been developed. In the present review, we summarize the recent progress in TJ-modulating peptides and discuss their potencies.
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