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

Abstract

Thiolated β-cyclodextrin (β-CD) has the potential to enhance mucoadhesive and permeation enhancing properties on ocular mucosa. Thiolated β-CD was synthesized via replacement of all primary hydroxyl groups on β-CD backbone by halogen followed by substitution with thiol groups. The structure was confirmed by FT-IR and 1H 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 β-CD displayed 5360 ± 412 µmol/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 β-CD exhibited a 5.3-fold improved aqueous solubility as compared to the unmodified β-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 β-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 β-CD might be a promising auxiliary agent for ocular drug delivery