PerspectiveStructural Biology

Breaking the intestinal barrier to deliver drugs

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Science  13 Feb 2015:
Vol. 347, Issue 6223, pp. 716-717
DOI: 10.1126/science.aaa6124

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Summary

Many drugs must be absorbed into the circulation for medicinal effects to occur at the intended sites of action, and so a holy grail of drug delivery is to improve the passage of pharmaceuticals across tissue barriers. Most oral drugs are absorbed in the small intestine, where the lumen is lined with epithelial cells. Thus, new therapeutic strategies for efficient oral delivery can benefit from a better understanding of the protein complexes, such as the tight junction, that maintain the integrity of this epithelium. On page 775 of this issue, Saitoh et al. (1) report the structure of a tight junction constituent called claudin-19, bound to a bacterial toxin called Clostridium perfringens enterotoxin (CPE), an agent that disrupts tight junctions and is a major cause of foodborne illness by this pathogen. The structural information may be useful in developing specific claudin-targeted compounds that improve drug delivery across tissue barriers that currently limit drug absorption.