Advances in the treatment of mycetoma: the emerging role of nanomedicine.

Mycetoma is a chronic, debilitating, neglected tropical disease characterized by a progressive subcutaneous infection caused by either fungi (eumycetoma) or bacteria (actinomycetoma), typically affecting the limbs, but no body part is immune. Current treatments remain limited, relying on long-term antifungal or antibiotic regimens that offer only modest efficacy, carry significant toxicity; and often surgical intervention is required. Drug-repurposing efforts, including computational screening and phenotypic assays, have identified several FDA-approved compounds with potential activity against Madurella mycetomatis. Moreover, newer antifungal agents such as fosravuconazole have shown efficacy comparable to or greater than itraconazole, the standard-of-care medication for mycetoma, with added practical advantages for use in endemic settings. For actinomycetoma, ongoing research continues to explore natural-product antibiotics and novel antimicrobial scaffolds that may inform future therapeutic options. Nanomedicine is emerging as a particularly promising approach to address the limitations of anti-infective therapies. While its application in mycetoma remains limited, nanotechnology-based systems have shown substantial benefits in other infectious diseases, suggesting significant potential for targeted, safer, and more effective therapy. This review summarizes current treatment challenges, advances in drug discovery and repurposing, and emerging nanomedicine approaches. Together, progress in these areas provides a foundation for developing improved and accessible therapies for mycetoma.