Amphotericin B: Insight into the advances in preclinical and clinical development

Abstract

Amphotericin B (AmB) is a recognized antifungal drug derived from a natural source that has been used for more than five decades to treat various fungal as well as protozoal infections. In the past two years, the drug has returned to the forefront of medical discussions as the preferred treatment for COVID-19-associated mucormycosis (CAM), popularly known as black fungus infections. AmB acts by binding to ergosterol present in the fungal cells resulting in the formation of pore ion channels and thus making the fungal cell membrane dysfunctional. It also produces free radicals inside fungal cells and thus impairs vital cellular pathways of the fungus. Low fungal resistance and broad-spectrum activity against an array of fungal species support the continued use of AmB for decades. However, nephrotoxicity produced by conventional formulations of AmB is a major limitation of their use and is the reason for the search for safer advanced lipid-based formulations and nano-formulations. The price of the medication with newer AmB formulations and the intravenous route of administration are the major obstacles to their widespread clinical use. Due to its significant toxicity, AmB is mainly used to treat life-threatening fungal infections and leishmaniasis only. This review provides an insight into the preclinical and clinical advancement of various AmB formulations, including its nano-formulations, promising for the therapy of susceptible infections in humans and animals.