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Effect of chitosan on epithelial permeability and structure
V Dodane1, M Amin Khan, J R Merwin
1The West Company Research Department, 101 Gordon Drive, Lionville, PA 19341-3012, USA. valerie_dodane@westpharma.com
International Journal of Pharmaceutics
|May 20, 1999
Summary
Chitosan enhances transmucosal drug delivery by reversibly altering intestinal epithelial cell permeability. It affects tight junctions and cell structure, but cells recover function with protein synthesis.
Area of Science:
- Biomaterials Science
- Cell Biology
- Pharmacology
Background:
- Chitosan is a mucoadhesive polymer with potential for enhancing transmucosal drug delivery.
- Understanding chitosan's impact on the intestinal mucosal barrier is crucial for optimizing drug delivery systems.
Purpose of the Study:
- To investigate the effects of chitosan on the function and structure of intestinal epithelial cells.
- To elucidate the mechanisms by which chitosan influences mucosal permeability.
Main Methods:
- Experiments were conducted using Caco-2 cell monolayers.
- Transepithelial electrical resistance and mannitol permeability were measured.
- Confocal scanning microscopy was used to visualize tight junction proteins (occludin, ZO-1) and actin.
- Cell viability was assessed using lactate dehydrogenase release and Trypan blue exclusion.
Main Results:
- Chitosan caused a reversible, dose-dependent decrease in transepithelial electrical resistance.
- Mannitol permeability increased, indicating compromised tight junctions.
- Chitosan altered the localization and intensity of occludin and ZO-1, and induced actin condensation.
- Cell recovery required protein synthesis, and plasma membrane integrity was slightly perturbed without affecting overall cell viability.
Conclusions:
- Chitosan enhances cell permeability through reversible effects on paracellular and intracellular pathways.
- These findings provide mechanistic insights into chitosan's role as a transmucosal drug delivery enhancer.