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.

Recent Advances in Nanomedicine for Ocular Fundus Neovascularization Disease Management

“…used glycol chitosan as a nanocarrier and 4‐carboxyphenylboronic acid pinacol ester as a ROS‐responsive group to encapsulate antifungal drug, voriconazole and then developed a ROS‐controlled release polymeric nanocarrier (GC‐EB) to treat fungal keratitis. [ 239 ] Unfortunately, the application of ROS‐responsive nanocarriers in FND management is almost a desert. Surprisingly, as an emerged oasis in the desert, Jiang et al.…”

Multifunctional nano-in-micro delivery systems for targeted therapy in fundus neovascularization diseases

“…These include NIMs carrying an agent cross-linked by visible light for corneal regeneration [23] and NIMs carrying peptide-drug conjugates (PDCs) with prolonged bioavailability to synergistically treat inflammation associated ocular disorders [24]. Other NIMs consist of polymeric nanocarriers bearing agents with reactive oxygen species (ROS) controlled release [25] and a versatile hybrid hydrogel. These NIMs have been found to exhibit the spatiotemporal properties allowing for drug release [26] in the treatment of infectious keratitis, and gene delivery by solid lipid NPs (SLNs) to treat X-linked juvenile retinoschisis [27].…”

Enhanced Intrusion of Exogenous Airborne Fine Particles toward Eyes in Humans and Animals: Where Damaged Blood–Ocular Barrier Plays a Crucial Role

“…Air pollution has become one of the key environmental crises, , associated with considerable detrimental human health outcomes. − Among air pollutants, ambient fine particles (AFPs, commonly known as fine particulate matter or PM 2.5 ) are gaining increasing attention in public health. − Strikingly, emerging studies suggested that the AFP pollution could not only affect the eye surface, such as eye discomfort, aberrant tear morphology, and ocular surface inflammation, but also have indirect adverse effects on the inner structures of eyes through inflammatory cytokines. − Liu et al previously reported the presence of black carbon particles at the ocular surface and found a positive association with dry eye disease . AFPs are laden with various pollutants (e.g., heavy meal, polycyclic aromatic hydrocarbons, and pathogens) and will transform once in the biological microenvironment, − generating reactive oxygen species (ROS) and bringing unpredicted health risks .…”