Non-ionic thiolated cyclodextrins - the next generation

Introduction: The current study was aimed at developing a novel mucoadhesive thiolated cyclodextrin (CD) without ionizable groups and an intact ring backbone for drug delivery. Materials and methods: Thiolated beta CD (beta-CD) was prepared through bromine substitution of its hydroxyl groups followed by replacement to thiol groups using thiourea. The thiolated beta-CD was characterized in vitro via dissolution studies, cytotoxicity studies, mucoadhesion studies on freshly excised porcine intestinal mucosa, and inclusion complex formation with miconazole nitrate. Results: Thiolated beta-CDs namely beta-CD-SH600 and beta-CD-SH1200 displayed 558.66 +/- 78 and 1,163.45 +/- 96 mu mol thiol groups per gram of polymer, respectively. Stability constant (Kc) of 190 M-1 confirmed the inclusion complex formation of miconazole nitrate with beta-CD-SH. Inclusion complexes of beta-CD-SH600 and beta-CD-SH1200 resulted in 157- and 257-fold increased solubility of miconazole nitrate, respectively. In addition, more than 80% of thiol groups were stable even after 6 hours at pH 5. Both beta-CD-SH compounds showed at least 1.3-fold improved solubility in water. In contrast to cationic thiolated CDs of the first generation, both thiomers showed no significant cytotoxicity. The mucoadhesive properties of the new thiolated CDs were 39.73-and 46.37-fold improved, respectively. Conclusion: These results indicate that beta-CD-SH might provide a new favorable tool for delivery of poorly soluble drugs providing a prolonged residence time on mucosal surfaces.