Development of nanodrug-based eye drops with good penetration properties and ROS responsiveness for controllable release to treat fungal keratitis

Abstract Fungal keratitis is challenging to diagnose and treat and remains a significant cause of blindness worldwide. The easiest and most common method of drug delivery for patients with fungal keratitis is eye drop administration. However, the therapeutic effect of traditional eye drops is unsatisfactory, largely due to the intrinsic nature of the ocular barriers, which limit drug absorption; the rapid decrease in the drug concentration caused by tears; and the side effects induced by the uncontrolled release of ocular drugs. Oxidative stress and inflammation are the main causes of corneal tissue necrosis in fungal keratitis, and reducing reactive oxygen species (ROS) and the inflammatory response are important goals in developing drugs for fungal keratitis. In the current study, we developed a ROS-responsive and controllable nanocarrier (GC-EB) that efficiently delivered a clinically used antifungal drug, voriconazole (VOR), to treat fungal keratitis. In vitro and in vivo results demonstrated that the developed GC-EB-VOR exhibited high penetration through corneal barriers, good retention in the cornea and controllable drug release under low concentrations of ROS. As a result, ROS were effectively depleted and the inflammatory response was inhibited; thus, GC-EB-VOR shows promising antifungal efficacy. This work may provide a new strategy for developing nanodrugs to improve the therapeutic effect of eye drop instillation on fungal keratitis and reduce the risk of blindness.