title: Improvement in the mucoadhesive properties of alginate by the covalent attachment of cysteine.
abstract: The purpose of the present study was to improve the mucoadhesive properties of alginate by the covalent attachment of cysteine. Mediated by a carbodiimide, L-cysteine was covalently linked to the polymer. The resulting thiolated alginate displayed 340.4+/-74.9 micromol thiol groups per g conjugate (means+/-S.D.; n=4). Within 2 h the viscosity of an aqueous mucus/alginate-cysteine conjugate mixture pH 7.0 increased at 37 degrees C by more than 50% compared to a mucus/alginate mixture, indicating enlarged interactions between the mucus and the thiolated polymer. Tensile studies carried out on freshly excised porcine intestinal mucosa demonstrated a total work of adhesion (TWA) of 25.8+/-0.6 and 101.6+/-36.1 microJ for alginate and the alginate-cysteine conjugate, respectively (means+/-S.D.; n=5). The maximum detachment force (MDF) was thereby in good correlation with the TWA. Due to the immobilization of cysteine, the swelling velocity of the polymer was significantly accelerated (P<0.05). In aqueous media the alginate-cysteine conjugate was capable of forming inter- and/or intramolecular disulfide bonds. Because of this crosslinking process within the polymeric network, the cohesive properties of the conjugate were also improved. Tablets comprising the unmodified polymer disintegrated within 49+/-14.5 min, whereas tablets of thiolated alginate remained stable for 148.8+/-39.1 min (means+/-S.D.; n=3). These features should render thiolated alginate useful as excipient for various drug delivery systems providing an improved stability and a prolonged residence time on certain mucosal epithelia.
authors: Institute of Pharmaceutical Technology and Biopharmaceutics, Center of Pharmacy, University of Vienna, Althanstr. 14, A-1090 Vienna, Austria. andreas.bernkop-schnuerch@univie.ac.at
authors: A
authors: A
authors: Bernkop-Schnürch
authors: C E
authors: CE
authors: Kast
authors: M F
authors: MF
authors: Richter
mesh_terms: D000268:Adhesiveness; D000464:Alginates / Q000737:chemistry*; D003545:Cysteine / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry; D009092:Mucous Membrane / Q000737:chemistry; D011108:Polymers; D012995:Solubility; D013438:Sulfhydryl Compounds / Q000032:analysis; D013607:Tablets; D013718:Tensile Strength; D014783:Viscosity
chemical_list: D000464:Alginates; D004220:Disulfides; D011108:Polymers; D013438:Sulfhydryl Compounds; D013607:Tablets; D003545:Cysteine