Fabrication of nanozyme-thixotropic anionic hydrogel coating with multi-enzyme-mimicking activity for the treatment of fungal keratitis

Fungal keratitis is the primary cause of infectious corneal blindness in China. Currently, early-stage treatment mainly involves the frequent administration of antifungal medications to ensure prolonged corneal contact and maintain effective drug concentration. This approach, however, may lead to harmful side effects and increased antifungal resistance due to the substantial use of antifungal agents. Consequently, the development of advanced antifungal strategies is essential. In the study, we fabricated a multi-enzyme-mimicking nanozyme-thixotropic anionic hydrogel coating (NHC) that incorporated voriconazole and copper-proanthocyanidins (CuPC) nanozyme, by the Schiff base reaction of self-synthesized polyaldehyde oligomer (PAO) with amino functionalized hyaluronic acid (AHA), for the treatment of fungal keratitis. The thixotropic anionic hydrogel significantly boosts the retention time and permeability of voriconazole, allowing a low dose to achieve a high therapeutic concentration. Additionally, the inherent antifungal and peroxidase-like activities of CuPC, coupled with the intrinsic characteristics of anionic hydrogel, further enhance the antifungal efficacy of NHC. Moreover, the NHC assists in corneal wound healing through stimulating cell proliferation by HA derivative as well as scavenging ROS via the catalase-like and superoxide dismutase-like activities of CuPC. The in vitro and in vivo studies have illustrated the safety and effectiveness of NHC, indicating its potential in the treatment of fungal keratitis.