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
Highlights
Chitosan (CS) is used as a novel carrier of drugs for oral and intravenous administration
The objective of the present study was to evaluate CS-salts solution of ethylenediaminetetraacetic acid (EDTA), HOBt, and thiamine pyrophosphate (TPP) for their in vitro absorption enhancement on transepithelial electrical resistance (TEER) and permeability of Caco-2 cells monolayers by using FITC-dextran (FD-4) as a model hydrophilic drug macromolecule; a secondary objective was to compare their cytotoxicity with that of CS aspartate which has been reported as an absorption enhancer[8]
At pH of 7.4, incubation on the apical side of the monolayer with the CS-salt solutions (0.001 – 1 %w/v) for 2 h resulted in no significant decrease(p < 0.05) in TEER for CS-A and CS-thiamine pyrophosphate (CSTPP) (Fig 3), but for CS-ethylene diamine tetraacetate (CS-EDTA) and CS-HOBt, there was concentration-dependent decrease (p < 0.05) in TEER at high concentrations
Summary
Chitosan (CS) is used as a novel carrier of drugs for oral and intravenous administration. The objective of the present study was to evaluate CS-salts solution of EDTA, HOBt, and TPP for their in vitro absorption enhancement on transepithelial electrical resistance (TEER) and permeability of Caco-2 cells monolayers by using FITC-dextran (FD-4) as a model hydrophilic drug macromolecule; a secondary objective was to compare their cytotoxicity with that of CS aspartate which has been reported as an absorption enhancer[8]. 2 %w/v of CS-salt solution was prepared by mixing the chitosan and the acids in water overnight at a ratio of 1:1 for chitosan thiamine pyrophosphate (CS-TPP) and chitosan hydroxybenzotriazole (CS-HOBt), 2:1 for chitosan ethylene diamine tetraacetate (CS-EDTA) and 1.5:1 for chitosan aspartate (CS-A). CS-salt solution was removed and fresh cell culture medium was added and incubated for 4 h to stabilize the cells.
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