A Natural Species-Based Supramolecular Hydrogel for Fungal Keratitis Treating with Anti-inflammatory and Biofilm Scavenging Multifunctions

Fungal infections pose a grave threat to visual health and may inflict irreversible damage and even blindness. Photothermal and photodynamic therapies have reached great achievements, however, their dependence on external light sources brings inconvenience for the treatment. Meanwhile, the treatments may cause side effects due to the high temperature during photothermal treatment and the excessive reactive oxygen species (ROS) from photodynamic treatment. Herein, a natural-species based antifungal nanodrug of TFCE NPs was prepared via one-step self-assemble of biogenic cinnamaldehyde (CA), tannic acids (TA), and ethylenediaminetetraacetic acid (EDTA) for topical fungal keratitis therapy. The in vivo and in vitro investigations validated that the TFCE NPs exhibited excellent antifungal activity against Candida albicans and anti-inflammation capability. Meanwhile, the TFCE NPs can effectively inhibit the formation of fungal biofilms and also eliminate mature biofilms. In vitro and in vivo safety assessments demonstrated that TFCE NPs exhibits excellent biocompatibility. To enhance ocular retention and bioavailability, a guanosine supramolecular hydrogel was developed in combination with TFCE NPs to formulate eye drops. The formulation was validated to have excellent therapeutic efficacy on mouse keratitis induced by Candida albicans . The developed strategy is free of light irradiation and avoids the effect of high temperature and ROS. The investigation offers a simple, low-cost, and efficient antifungal ophthalmic drop formulation with high biosafety for the treatment of fungal keratitis.