Totally S-protected hyaluronic acid: Evaluation of stability and mucoadhesive properties as liquid dosage form

• Published in: Carbohydrate polymers 2016-11, Vol.152, p.632-638
• Main Authors: Pereira de Sousa, Irene, Suchaoin, Wongsakorn, Zupančič, Ožbej, Leichner, Christina, Bernkop-Schnürch, Andreas
• Format: Article
• Language: English
• Subjects: Biological barrier; Liquid dosage form; Mucoadhesion; Preactivation; Thiolation
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2016.06.051

•Totally S-protected hyaluronic acid showing prolonged stability at physiological pH and under oxidative conditions could be successfully synthesized.•Totally S-protected hyaluronic acid showed a 52-fold higher viscosity when incubated with mucus compared to native hyaluronic acid.•The mucoadhesive properties of totally S-protected hyaluronic acid were confirmed by tensile test both in intestinal mucosa and palpebral conjunctiva.•Totally S-protected hyaluronic acid appears to be a promising excipient for the formulation of mucoadhesive liquid dosage forms. It is the aim of this study to synthesize hyaluronic acid (HA) derivatives bearing mucoadhesive properties and showing prolonged stability at pH 7.4 and under oxidative condition as liquid dosage form. HA was modified by thiolation with l-cysteine (HA-SH) and by conjugation with 2-mercaptonicotinic acid-l-cysteine ligand to obtain an S-protected derivative (HA-MNA). The polymers were characterized by determination of thiol group content and mercaptonicotinic acid content. Cytotoxicity, stability and mucoadhesive properties (rheological evaluation and tensile test) of the polymers were evaluated. HA-SH and HA-MNA could be successfully synthesized with a degree of modification of 5% and 9% of the total moles of carboxylic acid groups, respectively. MTT assay revealed no toxicity for the polymers. HA-SH resulted to be unstable both at pH 7.4 and under oxidative conditions, whereas HA-MNA was stable under both conditions. Rheological assessment showed a 52-fold and a 3-fold increase in viscosity for HA-MNA incubated with mucus compared to unmodified HA and HA-SH, respectively. Tensile evaluation carried out with intestinal and conjunctival mucosa confirmed the higher mucoadhesive properties of HA-MNA compared to HA-SH. According to the presented results, HA-MNA appears to be a potent excipient for the formulation of stable liquid dosage forms showing comparatively high mucodhesive properties.