title: The effect of the antioxidant on the properties of thiolated poly(aspartic acid) polymers in aqueous ocular formulations.
abstract: Thiolated polymers are a promising new group of excipients, but their stability against atmospheric oxidation has not been investigated in detail, and only a few efforts have been made to improve their stability. The oxidation of the thiol groups in solutions of thiolated polymers may result in a decrease of mucoadhesion and unpredictable in situ gelation. The aims of our work were to study the stability of aqueous solutions of thiolated polymers and the effects of stabilizing agents. We investigated thiolated poly(aspartic acid) polymers stabilized with dithiothreitol, glutathione or acetylcysteine. The effects of these antioxidants on the gel structure, mucoadhesion and drug release were determined by means of scanning electron microscopy, swelling, rheology, adhesion and drug release tests. It was concluded that the stability of polymer solutions containing antioxidants is sufficient for one day. Polymers stabilized with dithiotreitol demonstrated fast swelling and drug release, but weaker mucoadhesion as compared with the other samples. Polymers stabilized with glutathione displayed the weakest cohesive properties, resulting in fast and uncontrolled drug release and moderate mucoadhesion. Acetylcysteine-stabilized polymers exhibited an optimum cross-linked structure, with free thiol groups ensuring polymer-mucin interactions, resulting in the best mucoadhesive properties.
authors.affiliation: Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
authors.forename: Mária
authors.initials: M
authors.lastname: Budai-Szűcs
authors.affiliation: Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Horvát
authors.affiliation: Soft Matters Group, Department of Physical Chemistry and Materials Science, Budapest University of Technology and Economics, Műegyetem rkp. 3., H-1111 Budapest, Hungary.
authors.forename: Benjámin
authors.initials: B
authors.lastname: Gyarmati
authors.affiliation: Soft Matters Group, Department of Physical Chemistry and Materials Science, Budapest University of Technology and Economics, Műegyetem rkp. 3., H-1111 Budapest, Hungary.
authors.forename: Barnabás Áron
authors.initials: BÁ
authors.lastname: Szilágyi
authors.affiliation: Soft Matters Group, Department of Physical Chemistry and Materials Science, Budapest University of Technology and Economics, Műegyetem rkp. 3., H-1111 Budapest, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Szilágyi
authors.affiliation: Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
authors.forename: Szilvia
authors.initials: S
authors.lastname: Berkó
authors.affiliation: Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
authors.forename: Rita
authors.initials: R
authors.lastname: Ambrus
authors.affiliation: Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
authors.forename: Piroska
authors.initials: P
authors.lastname: Szabó-Révész
authors.affiliation: Department of Drug Sciences, Faculty of Pharmacy, University of Pavia, viale Taramelli 12, 27100 Pavia, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Sandri
authors.affiliation: Department of Drug Sciences, Faculty of Pharmacy, University of Pavia, viale Taramelli 12, 27100 Pavia, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Bonferoni
authors.affiliation: Department of Drug Sciences, Faculty of Pharmacy, University of Pavia, viale Taramelli 12, 27100 Pavia, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Caramella
authors.affiliation: Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary. Electronic address: csanyi@pharm.u-szeged.hu.
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Csányi
mesh_terms: D060433:Administration, Ophthalmic; D000975:Antioxidants / Q000737:chemistry*; D005123:Eye; D008855:Microscopy, Electron, Scanning; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry*; D012212:Rheology; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D010455:Peptides; D013438:Sulfhydryl Compounds; C017645:polyaspartate
keywords: Drug release; Mucoadhesion; Rheology; Stability; Thiolated polymer