Inflammation-responsive molecular-gated contact lens for the treatment of corneal neovascularization

Abstract

Corneal neovascularization (CNV) badly damages the corneal transparency, resulting in visual disturbance and blindness. The frequent administration of glucocorticoid eye drops in clinical increases the possibility of side effects and reduces patient compliance. Considering CNV is often accompanied by an increase in ROS production, a ROS-responsive monomer 2-(methylthio)ethyl methacrylate was introduced into the matrix as a “gating switch”. The prepared dexamethasone contact lenses (MCLs@Dex) showed a significant H2O2-responsive release for 168 h. To avoid corneal hypoxia and neovascularization caused by long-term wearing, high‑oxygen-permeability fluorosiloxane materials were incorporated. The oxygen permeability of MCLs@Dex was 4 times that of commercially available hydrogel contact lenses and had ultra-low protein adsorption, which meets the requirements of long-term wearing. In vivo pharmacokinetic studies showed that MCLs@Dex increased the mean residence time by 19.7 times and bioavailability by 2.29 times compared with eye drops, validating the ROS response and sustained release properties. More importantly, MCLs@Dex had satisfactory effects on reducing inflammation and decreasing the related cytokines and oxidative stress levels, and demonstrated significant inhibition of neovascularization, with a suppression rate of 76.53% on the 14th day. This responsive drug delivery system provides a promising new method for the safe and effective treatment of ocular surface diseases.