Enhanced Topical Antifungal Activity of an Isavuconazole Nanoparticles Loaded Cream Against Clinically Relevant Fungal Pathogens

Abstract

Superficial fungal infections continue to pose a significant therapeutic challenge due to their growing prevalence, recurring nature and emergence of antifungal resistance. Antifungal products in the topical environment have limited penetration and drug retention that can lead to the poor performance of the medicine. In this study, we investigated the in vitro antifungal properties of Isavuconazole nanoparticles-loaded cream for topical drug delivery and antifungal treatment in the skin. The nanoparticle-loaded cream was used in clinical studies on three important fungal pathogens, Candida albicans, Aspergillus niger, and Trichophyton rubrum with agar well diffusion. The effectiveness of the medication therapy was also tested with the minimum inhibitory concentration (MIC) analysis based on the broth microdilution method. The nanoparticle-loaded cream showed significantly higher zones of inhibition than the marketed antifungal cream on all fungal strains, and the highest concentration on Candida albicans was observed. The nanoparticle-loaded cream had lower MIC levels and thus had more antifungal activity. The plain cream base had no antifungal activity and hence the inhibition was due to the Isavuconazole. The nanoparticle-loaded cream has a better antifungal ability as it can penetrate more into the cells, interact with the infected tissue and release drug from the nanoparticulate carrier system. This indicates that the nanoparticle-mediated topical delivery substantially enhances the antifungal drug activity of Isavuconazole and is a promising approach for treating the superficial fungal infection. Further ex vivo, in vivo and clinical studies are recommended to assess the therapeutic benefits and long-term safety of the developed formulation.