Thiolated α-Cyclodextrin: The Invisible Choice to Prolong Ocular Drug Residence Time

It was the aim of this study to develop cysteamine-conjugated alpha-cyclodextrin (alpha-CD) enabled to form disulfide bonds with cysteine-rich substructures of the ocular mucus layer to provide a prolonged residence time of incorporated drugs at the site of action. Cysteamine was covalently attached to oxidized alpha-CD via reductive amination. The resulting alpha-CD-cysteamine conjugates (alpha-CD-Cys) were characterized regarding the amount of free thiol groups attached to the oligomer backbone via Ellman's reagent; resazurin assay was conducted for cytotoxicity, and mucoadhesive properties were evaluated on porcine intestinal and ocular mucosal tissues. Furthermore, albino rabbits were used for assessing the irritation-masking effects of alpha-CD-Cys. Free thiol groups attached to the backbone were in the range of 558 +/- 24-1143 +/- 92 mu mol/g. None of these alpha-CD-Cys unduly affected the viability of Caco-2 cells in a concentration of 0.5%. Mucoadhesive properties of alpha-CD-Cys were up to 32-fold improved compared to unmodified a-CD. Encapsulation of cetirizine into alpha-CD-Cys resulted in significantly reduced local ocular mucosal irritation of this model drug. According to these results, alpha-CD-Cys is a promising new tool to prolong drug residence time on the ocular mucosal surface. (C) 2016 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.