Khorsand Fatemeh, Hashemi Seyed Jamal, Mahmoudi Shahram, Kamali Sarvestani Hasti, Amani Amir
Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Mol Biotechnol. 2025 Jul 26. doi: 10.1007/s12033-025-01485-7.
Clotrimazole is widely used to treat fungal diseases, but it should be applied topically for several weeks to be effective. Previous studies have shown that nanoemulsions can enhance the topical activity of various active ingredients. This study aimed to prepare a nanoformulation of clotrimazole to improve its antifungal activity. A nanoemulsion containing clotrimazole was prepared using Tween 80 and Tween 20. The particle size was measured using Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM). Stability studies were conducted using freeze-thaw cycles and storage at 40 °C. The antifungal activity of clotrimazole was then compared with bulk clotrimazole both in vitro and in vivo. The nanoemulsion containing clotrimazole had a particle size of 31.5 nm, measured by DLS and remained physically stable after 1 year of storage. In vitro antifungal studies showed that this nanoemulsion outperformed both bulk clotrimazole and the nanoemulsion without clotrimazole, with MIC values of 1/524288, 1/8192, and 1/1024, respectively, against T. mentagrophytes. In addition, animal studies demonstrated that mean (SD) treatment time for fungal infection was 8.6 (0.5) days with the nanoemulsion containing 1% clotrimazole, significantly smaller than that of bulk clotrimazole (1% w/w) and nanoemulsion without clotrimazole (i.e., 15.0 (1.6) and 20.0 (0.7) days, respectively). The treatment time was more than 21 days for the bulk tea tree oil and the untreated control. After 21 days of treatment, only animals treated with the clotrimazole nanoemulsion showed complete lesion healing and weight changes comparable to healthy animals. The nanoemulsion formulation containing clotrimazole demonstrates highly desirable antifungal properties, warranting further investigation in clinical trials.
克霉唑广泛用于治疗真菌疾病，但应局部应用数周才有效。先前的研究表明，纳米乳剂可增强各种活性成分的局部活性。本研究旨在制备克霉唑的纳米制剂以提高其抗真菌活性。使用吐温80和吐温20制备了含克霉唑的纳米乳剂。通过动态光散射（DLS）和透射电子显微镜（TEM）测量粒径。使用冻融循环和在40℃下储存进行稳定性研究。然后在体外和体内将克霉唑的抗真菌活性与原料药克霉唑进行比较。含克霉唑的纳米乳剂通过DLS测量的粒径为31.5nm，储存1年后保持物理稳定。体外抗真菌研究表明，这种纳米乳剂的抗真菌性能优于原料药克霉唑和不含克霉唑的纳米乳剂，对须癣毛癣菌的最低抑菌浓度（MIC）值分别为1/524288、1/8192和1/1024。此外，动物研究表明，含1%克霉唑的纳米乳剂治疗真菌感染的平均（标准差）时间为8.6（0 .5）天，显著短于原料药克霉唑（1%w/w）和不含克霉唑的纳米乳剂（分别为15.0（1.6）天和20.0（0.7）天）。原料药茶树油和未治疗对照组的治疗时间超过21天。治疗21天后，只有用克霉唑纳米乳剂治疗的动物显示病变完全愈合，体重变化与健康动物相当。含克霉唑的纳米乳剂配方显示出非常理想的抗真菌特性，值得在临床试验中进一步研究。
