title: Thiolated alkyl-modified carbomers: Novel excipients for mucoadhesive emulsions.
abstract: The aim of this study was the design and evaluation of mucoadhesive emulsifying polymeric excipients. Three thiol bearing ligands with increasing pKa values of their sulfhydryl group, namely 4-aminothiophenol (pKa=6.86), l-cysteine (pKa=8.4) and d/l-homocysteine (pKa=10.0) were coupled to the polymeric backbone of alkyl-modified carbomer (PA1030). Resulting conjugates displayed 818.5μmol 4-aminothiophenol, 698.5μmol cysteine and 651.5μmol homocysteine per gram polymer and were evaluated regarding the reactivity of thiol groups, emulsifying and mucoadhesive properties. In general, the synthesized conjugates showed a pH dependent reactivity, whereby the fastest oxidation occurred in PA1030-cysteine, as almost no free thiol groups could be detected after 120min. Emulsification of medium chain triglycerides was feasible with all synthesized conjugates leading to oil-in-water-emulsions. Emulsions with PA1030-cysteine displayed the highest stability and the smallest droplet size among the tested formulations. Oxidation and consequently cross-linking of the thiomers prior to the emulsification process led to an overall decreased emulsion stability. Evaluating mucosal residence time of thiomer emulsions on porcine buccal mucosa, a 9.2-fold higher amount of formulation based on PA1030-cysteine remained on the mucosal tissue within 3h compared to the unmodified polymer. According to these results, the highest reactive ligand l-cysteine seems to be most promising in order to obtain thiolated polymers for the preparation of mucoadhesive o/w-emulsions.
authors: Center for Chemistry and Biomedicine, Center for Molecular Biosciences (CMBI), Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors: Sonja
authors: S
authors: Bonengel
authors: Center for Chemistry and Biomedicine, Center for Molecular Biosciences (CMBI), Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors: Sabine
authors: S
authors: Hauptstein
authors: Center for Chemistry and Biomedicine, Center for Molecular Biosciences (CMBI), Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors: Gintare
authors: G
authors: Leonaviciute
authors: ThioMatrix GmbH, Research Center, Trientlgasse 65, 6020 Innsbruck, Austria.
authors: Julia
authors: J
authors: Griessinger
authors: Center for Chemistry and Biomedicine, Center for Molecular Biosciences (CMBI), Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria. Electronic address: andreas.bernkop@uibk.ac.at.
authors: Andreas
authors: A
authors: Bernkop-Schnürch
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D000268:Adhesiveness; D000814:Aniline Compounds / Q000737:chemistry*; D000818:Animals; D018938:Caco-2 Cells; D003545:Cysteine / Q000737:chemistry*; D004655:Emulsions; D005079:Excipients / Q000737:chemistry*; D006710:Homocysteine / Q000737:chemistry*; D006801:Humans; D009061:Mouth Mucosa / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013552:Swine
chemical_list: D000180:Acrylic Resins; D000814:Aniline Compounds; D004655:Emulsions; D005079:Excipients; D013438:Sulfhydryl Compounds; C479038:carbomer; D006710:Homocysteine; C064316:4-aminothiophenol; D003545:Cysteine
keywords: Mucoadhesion; Mucoadhesive emulsions; Oil in water emulsions; Thiomers