Tetradeca-thiolated cyclodextrins: Highly mucoadhesive and in-situ gelling oligomers with prolonged mucosal adhesion

A highly mucoadhesive tetradeca-thiolated β-cyclodextrin (β-CD) was synthesized by replacement of all primary OH groups at C-6 position and all secondary OH groups at C-2 position of β-CD backbone via SH groups using a microwave-assisted method and to evaluate its rheological and mucoadhesive properties in-vitro.

Tetradeca-thiolated β-CD oligomer displayed 8144 ± 317 µmol thiol groups per gram. These thiol groups displaying a pKa value of 8.2 were stable at pH 4 but prone to oxidation at higher pH values. The newly synthesized thiolated CD did not show any cytotoxicity to Caco-2 cells at a concentration of 0.5% (m/v) within 24 h. Due to the addition of 0.5 and 2% (m/v) tetradeca-thiolated β-CD to mucus and keratin, the dynamic viscosity was increased up to 7.6- and 5.9- fold, respectively, within 4 h at 37 °C. Moreover, in-vitro mucoadhesion studies of tetradeca-thiolated CD showed 78.6-, 60.3-, 62.3- and 49.3- fold improved mucoadhesion on intestinal, buccal, bladder and vaginal mucosa as compared to unmodified β-CD, respectively.

According to these results, tetradeca-thiolated β-CD might be a promising auxiliary agent to provide a prolonged residence time of drug delivery systems on different mucosal surfaces.