title: Multifunctional adhesive polymers: Preactivated thiolated chitosan-EDTA conjugates.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Pharmaceutical Sciences, Faculty of Pharmacy, Thammasat University, Rungsit campus, Phahonyothin Rd., Khlong Luang, Pathumthani 12120, Thailand.
authors.forename: Kesinee
authors.initials: K
authors.lastname: Netsomboon
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors.forename: Wongsakorn
authors.initials: W
authors.lastname: Suchaoin
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors.forename: Flavia
authors.initials: F
authors.lastname: Laffleur
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors.forename: Felix
authors.initials: F
authors.lastname: Prüfert
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria. Electronic address: andreas.bernkop@uibk.ac.at.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002118:Calcium / Q000737:chemistry; D002412:Cations; D002448:Cell Adhesion; D002470:Cell Survival; D002614:Chelating Agents / Q000737:chemistry; D048271:Chitosan / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry; D016503:Drug Delivery Systems; D004492:Edetic Acid / Q000737:chemistry*; D006801:Humans; D007477:Ions; D008274:Magnesium / Q000737:chemistry; D009092:Mucous Membrane / Q000378:metabolism; D009539:Nicotinic Acids / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013552:Swine; D013607:Tablets; D013718:Tensile Strength
chemical_list: D002412:Cations; D002614:Chelating Agents; D004220:Disulfides; D007477:Ions; D009539:Nicotinic Acids; D011108:Polymers; D013438:Sulfhydryl Compounds; D013607:Tablets; D048271:Chitosan; D004492:Edetic Acid; C083470:2-mercaptonicotinic acid; D008274:Magnesium; D002118:Calcium
keywords: Chelation; Cytotoxicity; Mucoadhesive properties; Mucosal drug delivery; Preactivation; Thiolation