Chitosan-4-mercaptobenzoic acid: synthesis and characterization of a novel thiolated chitosan

Abstract

Thiomers are thiolated polymers with excellent mucoadhesive properties. The aim of this study was to synthesize a novel thiolated chitosan with higher reactivity in order to further improve mucoadhesion. For this purpose, 4-mercaptobenzoic acid was chosen to be covalently attached to chitosan. The aromatic structure of the ligand should exhibit a higher reactivity due to a comparatively low pK_a value of the thiol group, which was determined to be 6.8. Mucoadhesion, in situ gelation, biocompatibility and toxicity were evaluated. Chitosan-4-mercaptobenzoic acid was proved to be 60-fold more mucoadhesive compared to unmodified chitosan. After 24 hours, the viscosity of the novel thiomer solution increased 2974-fold compared to unmodified chitosan and after 48 hours 4487-fold. Chitosan-4-mercaptobenzoic acid tablets disintegrated twice as slowly as unmodified chitosan. Furthermore, the novel thiomer proved to be biodegradable and to be non-toxic. Due to the above mentioned properties, chitosan-4-mercaptobenzoic acid is a promising excipient for oral formulations or in situ gelling formulations.