Thiolated cyclodextrins: Mucoadhesive and permeation enhancing excipients for ocular drug delivery

Thiolated beta-cyclodextrin (beta-CD) has the potential to enhance mucoadhesive and permeation enhancing properties on ocular mucosa. Thiolated beta-CD was synthesized via replacement of all primary hydroxyl groups on beta-CD backbone by halogen followed by substitution with thiol groups. The structure was confirmed by FT-IR and H-1 NMR spectroscopy. Thiolated CD was characterized for hemolytic effect, ocular irritation, solubility enhancement, viscoelastic behavior and mucoadhesive properties. Moreover, the permeation enhancing effect of thiolated oligomer on different ocular tissues including conjunctiva, sclera and cornea was evaluated with sodium fluorescein (Na-Flu) as a marker. Thiolated beta-CD displayed 5360 +/- 412 mu mol/g thiol groups. The newly synthesized oligomer did not show any hemolytic effect on red blood cells at a concentration of 0.5% (m/v) for an incubation period of 3 h and minimal corneal irritation effects without any inflammation within 72 h. Thiolated beta-CD exhibited a 5.3-fold improved aqueous solubility as compared to the unmodified beta-CD. Thiolated oligomer (0.5% m/v) enhanced the viscosity of mucus up to 6.2-fold within 4 h and provided a 26-fold prolonged ocular residence time due to mucoadhesion. Moreover, 0.5% (m/v) thiolated beta-CD enhanced the permeation of Na-Flu 9.6-, 7.1- and 5.3-fold on conjunctiva, sclera and cornea, respectively. Based on these findings, thiolated beta-CD might be a promising auxiliary agent for ocular drug delivery.

Automated summary

Thiolated beta-cyclodextrin was synthesized and characterized for its potential use as an auxiliary agent for ocular drug delivery, showing enhanced permeation and mucoadhesive properties. The newly synthesized thiolated oligomer exhibited improved aqueous solubility, viscosity enhancement of mucus, prolonged ocular residence time, and enhanced permeation of sodium fluorescein on various ocular tissues, making it a promising candidate for ocular drug delivery.