Multifunctional adhesive polymers: Preactivated thiolated chitosan-EDTA conjugates

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• 作者：Kesinee Netsomboon^a ; Wongsakorn Suchaoin^b ; Flavia Laffleur^b ; Felix Prü ; fert^b ; Andreas Bernkop-Schnü ; rch^b ; ^{andreas.bernkop@uibk.ac.at}
• 关键词：Mucosal drug delivery ; Thiolation ; Preactivation ; Chelation ; Cytotoxicity ; Mucoadhesive properties
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：111
• 期：Complete
• 页码：26-32
• 全文大小：830 K
• 卷排序：111

文摘

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.MethodsThiol 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.ResultsDetermination 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 6 h while Ch-EDTA adhered for just 1 h.ConclusionAccording 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.