Synthesis and in vitro characterization of a novel S-protected thiolated alginate

The object of this study was to synthesize and characterize a novel S-protected thiolated polymer with a high degree of modification. In this regard, an alginate-cysteine and an alginate-cysteine-2-mercaptonicotinic acid conjugate were synthesized. To achieve a high coupling rate of the thiol group bearing ligand cysteine to the polymer, the carbohydrate was activated by an oxidative ring opening with sodium periodate followed by a reductive amination to bind the primary amino group of cysteine to resulting reactive aldehyde groups. The obtained thiolated polymer displayed 1561 +/- 130 mu mol thiol groups per gram polymer. About one third of these thiol groups were S-protected by the implementation of a thiol bearing aromatic protection group via disulfide bond formation. Test tablets of both modified polymers showed improved stability against oxidation in aqueous environment compared to the unmodified alginate and exhibit higher water-uptake capacity. Rheological investigations revealed an increased viscosity of the S-protected thiolated polymer whereat the thiolated non S-protected polymer showed gelling properties after the addition of hydrogen peroxide. The mucoadhesive properties could be improved significantly for both derivatives and no alteration in biocompatibility tested on Caco-2 cell monolayer employing an MTT assay could be detected after modification. According to these results, both new derivatives seem promising for various applications. (C) 2015 Elsevier Ltd. All rights reserved.