Advancing fungal keratitis treatment: transitioning from conventional amphotericin B therapy to nanocarrier-based delivery systems

Abstract

Fungal keratitis (FK) is a serious, vision-threatening ocular infection caused by various fungal species. Poor outcomes often leave patients with corneal opacification and loss of vision, occasionally advancing to enucleation due to the lack of effective treatment options. Several health agencies have outlined topical antifungal medications as first-line approaches in treating FK. Commercially available topical antifungal formulations are natamycin (5%), voriconazole (1%), fluconazole (0.2-0.5%), itraconazole (1%), and amphotericin B (0.15%). Different molecules remain effective against various species of fungus. However, amphotericin B (Am-B) is a broad-spectrum antifungal agent, and when all other medications fail, Am-B is the only drug of choice. However, its clinical application is hindered due to the non-availability of ophthalmic marketed products because of its poor pharmaco-technical factors (low solubility, poor permeation, unstable in solutions of pH 3-10, etc.). Therefore, clinicians are forced to use Am-B injectables off-label by preparing the diluted concentrations of Am-B for ophthalmic use. These solutions have limitations, viz., poor stability, rapid precorneal clearance, and limited drug retention. Thus, it is highly essential for the development of advanced ophthalmic novel drug delivery systems so that the therapeutic and toxic profiles of drugs might improve. Therefore, the present review explores the limitations of conventional Am-B therapy and highlights the transformative potential of nanocarrier-based delivery systems in FK management. It discusses various nanocarrier strategies, their pharmacokinetics, and preclinical and clinical advancements. By bridging the gap between conventional treatments and modern nanotechnology, this review underscores the potential of nanocarriers to revolutionize FK treatment, offering more effective and patient-friendly therapeutic solutions.

Keywords: Amphotericin B; Corneal ulcer; Fungal keratitis; Infection; Managemental strategy; Nanotechnology; Pathophysiology; Structural properties.