title: Thiolated and S-protected hydrophobically modified cross-linked poly(acrylic acid)--a new generation of multifunctional polymers.
abstract: The aim of this study was to create a novel multifunctional polymer by covalent attachment of l-cysteine to the polymeric backbone of hydrophobically modified cross-linked poly(acrylic acid) (AC1030). Secondly, the free thiol groups of the resulting thiomer were activated using 2-mercaptonicotinic acid (2-MNA) to provide full reactivity and stability. Within this study, 1167.36 μmol cysteine and 865.72 μmol 2-MNA could be coupled per gram polymer. Studies evaluating mucoadhesive properties revealed a 4-fold extended adherence time to native small intestinal mucosa for the thiomer (AC1030-cysteine) as well as an 18-fold prolonged adhesion for the preactivated thiomer (AC1030-Cyst-2-MNA) compared to the unmodified polymer. Modification of the polymer led to a higher tablet stability concerning the thiomer and the S-protected thiomer, but a decelerated water uptake could be observed only for the preactivated thiomer. Neither the novel conjugates nor the unmodified polymer showed severe toxicity on Caco-2 cells. Evaluation of emulsification capacity proofed the ability to incorporate lipophilic compounds like medium chain triglycerides and the preservation of the emulsifying properties after the modifications. According to these results thiolated AC1030 as well as the S-protected thiolated polymer might provide a promising tool for solid and semisolid formulations in pharmaceutical development.
authors: Center for Chemistry and Biomedicine, Center for Molecular Biosciences, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria.
authors: Sonja
authors: S
authors: Bonengel
authors: Center for Chemistry and Biomedicine, Center for Molecular Biosciences, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria.
authors: Sabine
authors: S
authors: Haupstein
authors: Center for Chemistry and Biomedicine, Center for Molecular Biosciences, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria.
authors: Glen
authors: G
authors: Perera
authors: Center for Chemistry and Biomedicine, Center for Molecular Biosciences, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria.
authors: Andreas
authors: A
authors: Bernkop-Schnürch
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D018938:Caco-2 Cells; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004655:Emulsions; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008422:Materials Testing; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013607:Tablets
chemical_list: D000180:Acrylic Resins; D003432:Cross-Linking Reagents; D004655:Emulsions; D013438:Sulfhydryl Compounds; D013607:Tablets; C006903:carbopol 940
keywords: C10–C30 alkyl acrylate cross polymers; Drug delivery; Mucoadhesion; Multifunctional polymers; Preactivated thiomers; Thiomers