Eshimy Rana, El-Batal Ahmed I, Mosallam Farag M
Microbiology and immunology, Egyptian drug authority, Cairo, Egypt.
Microbiology and Immunology department, Faculty of pharmacy, Ahram Canadian University, Giza, Egypt.
J Antibiot (Tokyo). 2025 May 29. doi: 10.1038/s41429-025-00831-w.
Traditional antifungal drugs are ineffective against multidrug-resistant Candida infections. The goal of this work is the preparation of Clotrimazole Selenium Nano-composite (CZ-Se-NC) suspension and CZ-Se-NC-gel for combating clotrimazole-resistant Candida albicans (NCRRT-CZR) infection. CZ-Se-NC is prepared by simple homogenization ultra-sonication technique and validated by SEM-EDX mapping, DLS, Zeta potential and FT-IR that confirm formulation of Nano-composite. In vitro results demonstrated that CZ-Se-NC and formulated CZ-Se-NC gel have the same anti-candidal activity showing inhibitory zone values 31.0 ± 0.931 mm, 27.0 ± 1.004 and MIC values 0.625, 1.25 µg ml and MFC values 2.5, 5 µg ml against C. albicans (ATCC 10231) and C. albicans (NCRRT-CZR), respectively. Non-treated C. albicans (NCRRT-CZR) show biofilm formation 100% that become 8.62% after treatment with CZ-Se-NC at 1/2MIC. Virulence genes ALS1, Plb1, CDR1 and ERG11 expression of C. albicans (NCRRT-CZR) were down regulated by 76.67, 87.06, 53.67 and 76.01%, respectively, after treatment with CZ-Se-NC. The CZ-Se-NC gel formula gradually releases clotrimazole and selenium 41 and 48% after 24 h, respectively. Furthermore, after deep dermal infections by C. albicans (NCRRT-CZR), treated mice exhibit excellent skin infection healing performance as evidenced by the significantly reduced inflammation and complete skin infection clearance after treatment with CZ-Se-NC gel. Gamma rays show a negative impact on the CZ-Se-NC size distribution. The formulation of CZ-Se-NC as a topical gel formulation could provide an opportunity to develop a cost-effective approach to achieve optimal therapeutic performance against resistant fungal infections at a much lower dose than is currently used. Additionally, it will enhance patient compliance by reducing the frequent application.
传统抗真菌药物对多重耐药念珠菌感染无效。本研究的目的是制备克霉唑硒纳米复合材料（CZ-Se-NC）混悬液和CZ-Se-NC凝胶，以对抗耐克霉唑白色念珠菌（NCRRT-CZR）感染。CZ-Se-NC通过简单的匀质超声技术制备，并通过扫描电子显微镜-能谱分析（SEM-EDX）图谱、动态光散射（DLS）、zeta电位和傅里叶变换红外光谱（FT-IR）进行验证，这些结果证实了纳米复合材料的形成。体外实验结果表明，CZ-Se-NC和所制备的CZ-Se-NC凝胶具有相同的抗念珠菌活性，对白色念珠菌（ATCC 10231）和白色念珠菌（NCRRT-CZR）的抑菌圈直径分别为31.0±0.931毫米、27.0±1.004毫米，最低抑菌浓度（MIC）分别为0.625、1.25微克/毫升，最低杀菌浓度（MFC）分别为2.5、5微克/毫升。未处理的白色念珠菌（NCRRT-CZR）生物膜形成率为100%，用1/2MIC浓度CZ-Se-NC处理后降至8.62%。用CZ-Se-NC处理后，白色念珠菌（NCRRT-CZR）的毒力基因ALS1、Plb1、CDR1和ERG11的表达分别下调了76.67%、87.06%、53.67%和76.01%。CZ-Se-NC凝胶配方在24小时后分别逐渐释放41%的克霉唑和48%的硒。此外，在白色念珠菌（NCRRT-CZR）引起深部皮肤感染后，用CZ-Se-NC凝胶治疗的小鼠表现出优异的皮肤感染愈合性能, 治疗后炎症明显减轻，皮肤感染完全清除。伽马射线对CZ-Se-NC的尺寸分布有负面影响。将CZ-Se-NC制成局部凝胶制剂，可能提供一个机会来开发一种经济有效的方法，以比目前使用剂量低得多的剂量实现对耐药真菌感染的最佳治疗效果。此外，它将通过减少频繁用药来提高患者的依从性。
