Peptide and protein delivery : modulation of the intestinal tight junctions using bacterial enterotoxins

van der Walle, Christopher F. and Schmidt, Elke; Van Der Walle, Chris, ed. (2011) Peptide and protein delivery : modulation of the intestinal tight junctions using bacterial enterotoxins. In: Peptide and Protein Delivery. Elsevier, London, pp. 195-219. ISBN 9780123849359

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Abstract

Targeting the intestinal paracellular pathway for peptide and protein delivery, by modulating the cell-cell tight junctions has become increasingly popular. Our understanding of the tight junction (tj) composition, such as the role of tj-associated proteins and biochemical signaling pathways, has allowed us to identify and develop novel tj modulators. Inspiration has come from bacteria such as Clostridium perfringens and Vibrio cholerae which release enterotoxins into the intestine to specifically alter the barrier function of the epithelium, and can be compared with sodium caprate, a clinically available absorption enhancer. Although these enterotoxins show promise for clinical application, not only in drug delivery but also celiac disease, there are still several hurdles to overcome. The molecular mechanisms underpinning the action of the bacterial enterotoxins on the tj, and the limits with regards to their capacity to enhance drug delivery, remain active areas of research.