Modulation of the intestinal tight junctions using bacterial enterotoxins

Christopher F. van der Walle, Elke Schmidt

Research output: Chapter in Book/Report/Conference proceedingChapter

4 Citations (Scopus)

Abstract

This chapter discusses the modulation of the intestinal tight junctions using bacterial enterotoxins. Epithelial cell sheets limit the movement of solutes through the intercellular space by forming tight junctions (tjs) between adjacent epithelial cells, and therefore act as the major barrier between the internal and external environment of the body. There are three transepithelial pathways for molecules to pass from the intestinal lumen to the bloodstream: the passive transcellular pathway, the carrier-mediated transcellular pathway, and the paracellular pathway. Physicochemical properties, such as hydrophobicity, allow a molecule to passively partition from the intestinal lumen through the lipid bilayer into the cell. Some hydrophilic molecules, such as sugars and amino acids, are absorbed by specifically interacting with active transport systems on the cell membrane. Drug delivery via the paracellular pathway is less dependent on the physicochemical properties of the drug, and does not require a specific interaction with a transport system, and so is suitable for a large variety of molecules including peptides and proteins. Since opening of the tjs can cause the influx of other foreign substances, absorption enhancers acting via the paracellular pathway are required to modify the tight junctional structure reversibly. Early development of paracellular absorption enhancers was limited due to the lack of knowledge regarding the composition of the tjs and their regulatory role, resulting in unacceptable side-effects. Study of canonical enterotoxins (a class of exotoxin that acts on the intestinal epithelium) such as those released by Clostridium perfringens and Vibrio cholerae has increased our understanding to the point where one can exploit their mechanisms to facilitate peptide and protein delivery via the paracellular pathway.
LanguageEnglish
Title of host publicationPeptide and Protein Delivery
EditorsChris F. van der Walle
Place of PublicationLondon
Pages195-220
Number of pages26
DOIs
Publication statusPublished - 12 May 2011

Fingerprint

Tight Junctions
Enterotoxins
Transcytosis
Epithelial Cells
Sugar Acids
Exotoxins
Peptides
Clostridium perfringens
Vibrio cholerae
Active Biological Transport
Extracellular Space
Lipid Bilayers
Intestinal Mucosa
Hydrophobic and Hydrophilic Interactions
Pharmaceutical Preparations
Proteins
Cell Membrane
Amino Acids

Keywords

  • peptide and protein based materials
  • tight Junctions
  • drug delivery
  • Zonula Occludens-1 Protein

Cite this

van der Walle, C. F., & Schmidt, E. (2011). Modulation of the intestinal tight junctions using bacterial enterotoxins. In C. F. van der Walle (Ed.), Peptide and Protein Delivery (pp. 195-220). London. https://doi.org/10.1016/B978-0-12-384935-9.10009-4
van der Walle, Christopher F. ; Schmidt, Elke. / Modulation of the intestinal tight junctions using bacterial enterotoxins. Peptide and Protein Delivery. editor / Chris F. van der Walle. London, 2011. pp. 195-220
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van der Walle, CF & Schmidt, E 2011, Modulation of the intestinal tight junctions using bacterial enterotoxins. in CF van der Walle (ed.), Peptide and Protein Delivery. London, pp. 195-220. https://doi.org/10.1016/B978-0-12-384935-9.10009-4

Modulation of the intestinal tight junctions using bacterial enterotoxins. / van der Walle, Christopher F.; Schmidt, Elke.

Peptide and Protein Delivery. ed. / Chris F. van der Walle. London, 2011. p. 195-220.

Research output: Chapter in Book/Report/Conference proceedingChapter

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van der Walle CF, Schmidt E. Modulation of the intestinal tight junctions using bacterial enterotoxins. In van der Walle CF, editor, Peptide and Protein Delivery. London. 2011. p. 195-220 https://doi.org/10.1016/B978-0-12-384935-9.10009-4