Synergistic Antifungal Efficacy of Eugenol‐Loaded Nanocapsules Combined With Itraconazole Against Trichophyton mentagrophytes

Abstract

ABSTRACT Background and Objectives The increasing prevalence of dermatophyte infections and the emergence of antifungal resistance highlight the urgent need for novel treatment approaches. Trichophyton mentagrophytes, a common dermatophyte, often resists standard antifungal therapies, necessitating alternative solutions. Eugenol, a natural compound with potent antifungal properties, has gained attention for its synergistic effects with conventional antifungal agents. However, its clinical application is limited by poor bioavailability and stability. Nanoencapsulation of eugenol offers a promising strategy to enhance its antifungal efficacy and address these limitations. This study aims to evaluate the antifungal efficacy of eugenol and nanoencapsulated eugenol in combination with Itraconazole against T. mentagrophytes isolates. Methods Eugenol‐loaded nanocapsules were fabricated using the nanoprecipitation method and subsequently evaluated. The antifungal activity of eugenol, nano‐eugenol and Itraconazole—individually and in combination—was assessed against clinical isolates of T. mentagrophytes derived from animal and human sources, using minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) determinations. The chequerboard assay evaluated the synergistic effects. Results Scanning electron microscopy (SEM) and dynamic light scattering (DLS) analyses showed that eugenol nanocapsules have a uniform, spherical morphology with an average size of 150.9 nm and moderate polydispersity (polydispersity index [PDI] = 0.531), whereas a slight negative zeta potential (−0.1 mV) contributes to suspension stability by minimizing aggregation. The geometric mean MIC of eugenol was 119.3 µg/mL, significantly lower than that of nano‐eugenol (477.4 µg/mL), whereas Itraconazole had the lowest MIC at 11 µg/mL. Eugenol demonstrated a more potent fungicidal effect than its nanoencapsulated form, though nanoencapsulation improved stability and bioavailability. Combining Itraconazole with nano‐eugenol showed synergy in 73.3% of T. mentagrophytes isolates, reducing Itraconazole's MIC by up to 1/2 or 1/4. Both forms of eugenol exhibited effective anti‐dermatophytic activity. Conclusion The findings suggest that nanoencapsulated eugenol, in combination with Itraconazole, provides a potent and synergistic antifungal approach against T. mentagrophytes, potentially reducing the dosage and resistance risks associated with Itraconazole. These results underscore the potential of nano‐enhanced plant extracts in developing effective, sustainable antifungal therapies.

Keywords

• antifungal synergy | combination therapy | eugenol‐loaded nanocapsules | Itraconazole | nanoencapsulation | Trichophyton mentagrophytes