Malakootikhah Javad, Sharifzadeh Aghil, Rastegar Mohana, Khosravi Alireza, Nikaein Donya
Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
Department of Microbiology and Immunology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
Vet Med Sci. 2025 May;11(3):e70352. doi: 10.1002/vms3.70352.
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.
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.
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.
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.
皮肤癣菌感染的患病率不断上升以及抗真菌耐药性的出现凸显了对新型治疗方法的迫切需求。须癣毛癣菌是一种常见的皮肤癣菌，常常对标准抗真菌疗法产生耐药性，因此需要其他解决方案。丁香酚是一种具有强大抗真菌特性的天然化合物，因其与传统抗真菌药物的协同作用而受到关注。然而，其临床应用受到生物利用度低和稳定性差的限制。丁香酚的纳米包封提供了一种有前景的策略，可增强其抗真菌功效并解决这些限制。本研究旨在评估丁香酚和纳米包封丁香酚与伊曲康唑联合对须癣毛癣菌分离株的抗真菌功效。
采用纳米沉淀法制备负载丁香酚的纳米胶囊并随后进行评估。使用最低抑菌浓度（MIC）和最低杀菌浓度（MFC）测定法，分别评估丁香酚、纳米丁香酚和伊曲康唑单独及联合对来自动物和人类来源的须癣毛癣菌临床分离株的抗真菌活性。棋盘法评估协同效应。
扫描电子显微镜（SEM）和动态光散射（DLS）分析表明，丁香酚纳米胶囊具有均匀的球形形态，平均粒径为150.9 nm，多分散性适中（多分散指数[PDI]=0.531），而轻微的负zeta电位（-0.1 mV）通过最小化聚集有助于悬浮稳定性。丁香酚的几何平均MIC为119.3 μg/mL，显著低于纳米丁香酚（477.4 μg/mL），而伊曲康唑的MIC最低，为11 μg/mL。尽管纳米包封提高了稳定性和生物利用度，但丁香酚表现出比其纳米包封形式更强的杀菌作用。伊曲康唑与纳米丁香酚联合在73.3%的须癣毛癣菌分离株中显示出协同作用，将伊曲康唑的MIC降低高达1/2或1/4。两种形式的丁香酚均表现出有效的抗皮肤癣菌活性。
研究结果表明，纳米包封丁香酚与伊曲康唑联合提供了一种针对须癣毛癣菌的强效且协同的抗真菌方法，可能降低与伊曲康唑相关的剂量和耐药风险。这些结果强调了纳米增强植物提取物在开发有效、可持续抗真菌疗法方面的潜力。
