A novel clotrimazole selenium nano-composite for combating deep dermal Candida albicans infections and virulence...

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^-1 and MFC values 2.5, 5 µg ml^-1 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.