title: Preactivated thiolated poly(methacrylic acid-co-ethyl acrylate): synthesis and evaluation of mucoadhesive potential.
abstract: The study was aimed to developed and investigate a novel polymer for intestinal drug delivery with improved mucoadhesive properties. Therefore Eudragit® L 100-55 (poly(methacrylic acid-co-ethyl acrylate)) was thiolated by covalent attachment of L-cysteine. The immobilized thiol groups were preactivated by disulfide bond formation with 2-mercaptonicotinic acid. Resulting derivative (Eu-S-MNA) was investigated in terms of mucoadhesion via three different methods: tensile studies, rotating cylinder studies and rheological synergism method, as well as water-uptake capacity and cytotoxicity. Different derivatives were obtained with increasing amount of bound L-cysteine (60, 140 and 266 μmol/g polymer) and degree of preactivation (33, 45 and 51 μmol/g polymer). Tensile studies revealed a 30.5-, 35.3- and 52.2-fold rise of total work of adhesion for the preactivated polymers compared to the unmodified Eudragit. The adhesion time on the rotating cylinder was prolonged up to 17-fold in case of thiolated polymer and up to 34-fold prolonged in case of the preactivated polymer. Rheological synergism revealed remarkable interaction of all investigated modified derivatives with mucus. Further, water-uptake studies showed an over 7h continuing weight gain for the modified polymers whereat disintegration took place for the unmodified polymer within the first hour. Cell viability studies revealed no impact of modification. Accordingly, the novel preactivated thiolated Eudragit-derivative seems to be a promising excipient for intestinal drug delivery.
authors.affiliation: Center for Chemistry and Biomedicine, Center for Molecular Biosciences, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hauptstein
authors.affiliation: Center for Chemistry and Biomedicine, Center for Molecular Biosciences, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors.forename: Sonja
authors.initials: S
authors.lastname: Bonengel
authors.affiliation: Center for Chemistry and Biomedicine, Center for Molecular Biosciences, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Rohrer
authors.affiliation: Center for Chemistry and Biomedicine, Center for Molecular Biosciences, 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: D000180:Acrylic Resins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000268:Adhesiveness / Q000187:drug effects; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D000180:Acrylic Resins; C446821:Eudragit L100-55; D013438:Sulfhydryl Compounds
keywords: 2-Mercaptonicotinic acid (PubChem CID: 673681); Eudragit L 100-55; Eudragit® L 100-55; L-cysteine (PubChem CID: 5862); Mucoadhesion; Preactivated thiomer