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  • Title: Multifunctional adhesive polymers: Preactivated thiolated chitosan-EDTA conjugates.
    Author: Netsomboon K, Suchaoin W, Laffleur F, Prüfert F, Bernkop-Schnürch A.
    Journal: Eur J Pharm Biopharm; 2017 Feb; 111():26-32. PubMed ID: 27865931.
    Abstract:
    AIM: The aim of this study was to synthesis preactivated thiolated chitosan-EDTA (Ch-EDTA-cys-2MNA) conjugates exhibiting in particular high mucoadhesive, cohesive and chelating properties. METHODS: Thiol groups were coupled with chitosan by carbodiimide reaction and further preactivated by attachment with 2-mercaptonicotinic acid (2MNA) via disulfide bond formation. Determinations of primary amino and sulfhydryl groups were performed by TNBS and Ellman's tests, respectively. Cytotoxicity was screened by resazurin assay in Caco-2 cells. Mucoadhesive properties and bivalent cation binding capacity with Mg2+ and Ca2+ in comparison to chitosan-EDTA (Ch-EDTA) and thiolated Ch-EDTA (Ch-EDTA-cys) were evaluated. RESULTS: Determination of 2MNA and total sulfhydryl groups indicated that 80% of thiol groups were preactivated. The results from cytotoxicity studies demonstrated that Ch-EDTA-cys and Ch-EDTA-cys-2MNA were not toxic to the cells at the polymer test concentration of 0.25% (w/v) while cell viability decreased by increasing the concentration of Ch-EDTA. Although EDTA molecule was modified by thiolation and preactivation, approximately 50% of chelating properties of the conjugates were maintained compared to Ch-EDTA. Ch-EDTA-cys-2MNA adhered on freshly excised porcine intestinal mucosa up to 6h while Ch-EDTA adhered for just 1h. CONCLUSION: According to the combination of mucoadhesive and chelating properties of the conjugates synthesized in this study, Ch-EDTA-cys-2MNA might be useful for various mucosal drug delivery systems.
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