Thiolated Cyclodextrin: Development of a Mucoadhesive Vaginal Delivery System for Acyclovir

The objective of this study was the development of a mucoadhesive vaginal delivery system for acyclovir (Acv). Sodium-per-iodate (NaIO4) was used to introduce aldehyde substructures into beta-cyclodextrin (beta-CD) by oxidative cleavage of vicinal diol bonds. Cysteamine was covalently attached to beta-CD-CHO via reductive amination. Ellman's reagent was utilized for quantification of free thiol groups attached and resazurin assay was used for cytotoxicity studies. Mucoadhesive properties were evaluated on porcine vaginal mucosa in comparison to intestinal mucosa. Quantification of thiol groups revealed 851.84 +/- 107, 1040.44 +/- 132, and 1563.72 +/- 171 mu mol/g of free thiol groups attached to the beta-CD-SH851, beta-CD-SH1040, and beta-CD-SH1563, respectively. beta-CD-SH derivatives at concentrations of 0.5% (m/v) did not show significant reduction of viability of Caco-2 cells within 24 h. Furthermore, water solubility of beta-CD-SH1563 was improved 7.6-fold in comparison to unmodified beta-CD. beta-CD-SH851, beta-CD-SH1040, and beta-CD-SH1563 showed 5.84-, 15.95-, and 17.14-fold improved mucoadhesive properties on porcine vaginal mucosa and 3-, 12.47-, and 32.13-fold on porcine intestinal mucosa, respectively. Inclusion complex of Acv with beta-CD-SH1563 resulted in significantly improved drug dissolution. According to the results, beta-CD-SH derivatives might be promising new tools for local vaginal delivery of Acv. (C) 2016 American Pharmacists Association r. Published by Elsevier Inc. All rights reserved.