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<p>Dermatophytosis is a common fungal infection caused by dermatophytes, often resistant to conventional antifungal drugs like terbinafine and triazoles. Menthol, a plant-derived antifungal agent, offers potential when combined with standard drugs. Nanoencapsulation enhances menthol's stability, bioavailability, and antifungal efficacy. This study investigates the antifungal effects of pure and nanoencapsulated menthol in combination with voriconazole against human and animal <i>Trichophyton mentagrophytes</i> isolates. It aims to evaluate the synergistic potential and address resistance challenges in dermatophyte infections. Menthol-loaded nanocapsules were prepared via a nanoprecipitation method and characterized using Zeta Potential Analysis, Dynamic Light Scattering (DLS), and Scanning Electron Microscopy (SEM). Antifungal activity against 15 clinical <i>T. mentagrophytes</i> isolates was evaluated using Clinical and Laboratory Standards Institute (CLSI) -compliant microdilution and checkerboard assays, determining minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), and fractional inhibitory concentration index (FICI) values for menthol, nanoencapsulated menthol, and voriconazole. Statistical analysis assessed differences in antifungal efficacy. Menthol-loaded nanocapsules were predominantly rod-shaped with an average size of 300&#xa0;nm, stable zeta potential (-0.5&#xa0;mV), and low polydispersity (PDI: 0.549) confirming their suitability for antifungal applications. Nanoencapsulated menthol exhibited higher MIC (1979.26&#xa0;μg/mL) and MFC (4145.74&#xa0;μg/mL) than pure menthol, indicating reduced fungicidal potency. All <i>T. mentagrophytes</i> isolates demonstrated resistance to voriconazole, with human-derived isolates showing exceptionally high resistance levels. Synergistic effects were observed in 100% of isolates with nanoencapsulated menthol and voriconazole (FICI: 0.34 ± 0.11), outperforming non-encapsulated menthol (FICI: 0.47 ± 0.1). Nanoencapsulation significantly enhanced menthol's antifungal efficacy. Nanoencapsulated menthol synergistically enhances voriconazole's efficacy against <i>T. mentagrophytes</i>, offering a promising approach to reducing drug resistance. These findings highlight the potential of nanoencapsulation for antifungal therapy, warranting further in vivo and clinical studies.</p>

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Synergistic Effects of Nanoencapsulated Menthol and Voriconazole in Combating Trichophyton mentagrophytes in Human and Animal Isolates

  • 期刊论文

  • 发表日期：

    2026年3月5日

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  • Javad Malakootikhah,
  • Aghil Sharifzadeh,
  • Mohammadreza Alinouri,
  • Ali Reza Khosravi,
  • Hojjatollah Shokri

摘要

Dermatophytosis is a common fungal infection caused by dermatophytes, often resistant to conventional antifungal drugs like terbinafine and triazoles. Menthol, a plant-derived antifungal agent, offers potential when combined with standard drugs. Nanoencapsulation enhances menthol's stability, bioavailability, and antifungal efficacy. This study investigates the antifungal effects of pure and nanoencapsulated menthol in combination with voriconazole against human and animal Trichophyton mentagrophytes isolates. It aims to evaluate the synergistic potential and address resistance challenges in dermatophyte infections. Menthol-loaded nanocapsules were prepared via a nanoprecipitation method and characterized using Zeta Potential Analysis, Dynamic Light Scattering (DLS), and Scanning Electron Microscopy (SEM). Antifungal activity against 15 clinical T. mentagrophytes isolates was evaluated using Clinical and Laboratory Standards Institute (CLSI) -compliant microdilution and checkerboard assays, determining minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), and fractional inhibitory concentration index (FICI) values for menthol, nanoencapsulated menthol, and voriconazole. Statistical analysis assessed differences in antifungal efficacy. Menthol-loaded nanocapsules were predominantly rod-shaped with an average size of 300 nm, stable zeta potential (-0.5 mV), and low polydispersity (PDI: 0.549) confirming their suitability for antifungal applications. Nanoencapsulated menthol exhibited higher MIC (1979.26 μg/mL) and MFC (4145.74 μg/mL) than pure menthol, indicating reduced fungicidal potency. All T. mentagrophytes isolates demonstrated resistance to voriconazole, with human-derived isolates showing exceptionally high resistance levels. Synergistic effects were observed in 100% of isolates with nanoencapsulated menthol and voriconazole (FICI: 0.34 ± 0.11), outperforming non-encapsulated menthol (FICI: 0.47 ± 0.1). Nanoencapsulation significantly enhanced menthol's antifungal efficacy. Nanoencapsulated menthol synergistically enhances voriconazole's efficacy against T. mentagrophytes, offering a promising approach to reducing drug resistance. These findings highlight the potential of nanoencapsulation for antifungal therapy, warranting further in vivo and clinical studies.