Abstract

Fungal keratitis is a sight-threatening corneal infection affecting over a million people annually. Natamycin, a polyene extracted from Streptomyces natalensis, remains the only FDA-approved drug for the treatment of fungal keratitis. The conventional treatment involves 5% ophthalmic solution of natamycin, which is administered at a high frequency during the initial treatment phase and subsequently reduced in a tapering manner based on the observed clinical response. Although it demonstrates a broad spectrum of activity, its efficacy is hindered by limited corneal penetration attributed to its considerable molecular weight and low aqueous solubility.
This review consolidates current knowledge on fungal keratitis, including prevalence, risk factors, and etiology. It provides a comprehensive evaluation of natamycin, covering its pharmacology, mechanism of action, antifungal spectrum, and clinical applications while addressing the limitations of conventional natamycin therapy and ocular barriers that restrict drug delivery. Furthermore, the review highlights recent advances in both nanotechnology-based and non-nanotechnology-based natamycin delivery strategies aimed at enhancing corneal bioavailability.
Despite promising preclinical outcomes in terms of bioavailability and retention, no alternative natamycin formulations have yet progressed to clinical trials or commercialization. Further efforts are required to advance these delivery systems into clinical trials and realize their potential in improving outcomes for fungal keratitis.

Key words: Natamycin, fungal keratitis, novel drug delivery systems, ocular drug delivery, translational challenges