Mucoadhesive polymers: Design of S-protected thiolated cyclodextrin-based hydrogels

This study aims to design chemically crosslinked thiolated cyclodextrin-based hydrogels and to evaluate their mucoadhesive properties via mucosal residence time studies on porcine small intestinal mucosa and on porcine buccal mucosa.

Free thiol groups of heptakis(6-deoxy-6-thio)-β-cyclodextrin (β-CD-SH) were S-protected with 2-mercaptoethanesulfonic acid (MESNA) followed by crosslinking with citric acid. Cytotoxicity was assessed by hemolysis as well as resazurin assay. Hydrogels were characterized by their rheological and mucoadhesive properties. Ritonavir was employed as model drug for in vitro release studies from these hydrogels.

The structure of S-protected β-CD-SH was confirmed by IR and ¹H NMR spectroscopy. Degree of thiolation was 390 ± 7 µmol/g. Hydrogels based on native β-CD showed hemolysis of 12.5 ± 2.5 % and 13.6 ± 2.7 % within 1 and 3 h, whereas hemolysis of just 3.5 ± 2.8 % and 3.9 ± 3.0 % was observed for the S-protected thiolated CD hydrogels, respectively. Both native and S-protected thiolated hydrogels showed minor cytotoxicity on Caco-2 cells. Rheological investigations of S-protected thiolated β-CD-based hydrogel (16.2 % m/v) showed an up to 13-fold increase in viscosity in contrast to the corresponding native β-CD-based hydrogel. Mucosal residence time studies showed that thiolated β-CD-based hydrogel is removed to a 16.6- and 2.4-fold lower extent from porcine small intestinal mucosa and porcine buccal mucosa in comparision to the native β-CD-based hydrogel, respectively. Furthermore, a sustained release of ritonavir from S-protected thiolated β-CD-based hydrogels was observed.

Because of their comparatively high mucoadhesive and release-controlling properties, S-protected thiolated β-CD-based hydrogels might be promising systems for mucosal drug delivery.