Effect of Salt Forms of Chitosan on In Vitro Permeability Enhancement in Intestinal Epithelial Cells (Caco-2)
Abstract
Purpose: To investigate the effect of chitosan (CS) salt forms and pH condition on the transepithelial electrical resistance (TEER) of Caco-2 cell monolayer for enhanced permeability.
Methods: Solutions (2 %w/v) of four different salt forms of CS-aspartate (CS-A), CS-ethylene diamine tetraacetate (CS-EDTA), CS-hydroxybenzotriazole (CS-HOBt) and CS-thiamine pyrophosphate (CSTPP) - were prepared and tested on TEER using fluorescein isothiocyanate dextran 4,400 (FD-4) as the permeant across Caco-2 cell monolayer in both pH 6.2 and 7.4 (physiological pH) environment.
Results: The results show that CS-salt solutions, at pH of 6.2, increased cell permeability in a dosedependent manner and caused relatively reversible effects only at low doses of 0.001 - 0.010 %w/v. At CS-salt solution concentration of 0.01 %w/v, accumulation of FD-4 in the acceptor compartment was in the rank order: CS-EDTA > CS-TPP > CS-A > CS-HOBt. All CS-salt solutions significantly (p < 0.05) increased the transport of FD-4. On the other hand, at pH 7.4, only CS-EDTA at a concentration of 0.5 %w/v enhanced the transport of FD-4. CS-EDTA was also the most toxic CS salt.
Conclusion: The salt forms of CS are capable of enhancing the transport of FD-4 across Caco-2 cell monolayer, with CS-EDTA the most promising of them.
Keywords: Chitosan salts, Fluorescein isothiocyanate dextran, Transport, Absorption enhancer, Caco-2 cells
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