Ethosomal Nanoformulations for Combinational Photothermal Therapy of Fungal Keratitis

Fungal keratitis/mycotic keratitis or keratomycosis, is characterized by the inflammation of underlying stroma of corneal epithelium due to fungal infection. Multi-drug resistance and subsequent recurrence of infection limits the clinical outcomes of anti-fungal agents such as Amphotericin B and Natamycin; and therefore, demands research on newer anti-microbial strategies. In this study, the authors have synthesized and characterized ethosomes (IAEs) encapsulating a NIR dye, Indocyanine green (ICG), and an anti-fungal drug, Amphotericin B, for a combinational photothermal therapy of fungal keratitis. The in vitro anti-fungal efficacy of the IAEs is validated against Candida albicans by colony formation assay, calcofluor staining, and SEM analysis. The results indicate that the IAEs, upon NIR irradiation, displays a synergistic anti-fungal efficacy. The IAEs are highly biocompatible when tested using a human corneal epithelial (HCE) cell line model (in vitro) and a Draize eye test model in rabbits (in vivo). Further, it is observed that the IAEs,upon NIR laser exposure significantly eliminate the fungal infection in rat model of occular fungal keratitis. The research indicates that the IAEs nano-formulation exhibits a synergistic and sustained anti-fungal effect paving its way for further translation from bench to bedside for the efficient management of fungal keratitis.