Silver secnidazole nano-hybrid emulsion-based probiotics as a novel antifungal formula against multidrug-resistant vaginal pathogens

This study presents a novel approach to manage vaginal infections due to Candidiasis, utilizing a novel silver secnidazole nano-hybrid emulsion (Ag-Secn-NHE)-based probiotics and free Ag-Secn-NHE. Ag-Secn-NHE was prepared by simple homogenization‒ultrasonication technique and validated by using a ultraviolet‒visible scan, dynamic light scattering, transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy, and zeta potential. Saccharomyces cerevisiae (RCMB 002Y001) is the most effective probiotic-producing organism that demonstrates significant effects when combined with Ag-Secn-NHE. Ag-Secn-NHE-based probiotics showed significant antifungal effect compared to free Ag-Secn-NHE, silver nitrate, silver nanoparticles, secnidazole, secnidazole nanoemulsion, and commercial vaginal wash against multidrug-resistant vaginal pathogens. The highest inhibitory effect was achieved with Ag-Secn-NHE-based probiotic against Candida auris, Candida albicans, and Cryptococcus neoformans with minimal inhibitory concentration (MIC) 0.625 ± 0.002, 0.00625:1.25 ± 0.012 and 0.00625:1.25 ± 0.032 mg/mL, respectively, in comparison with Ag-Secn-NHE that show MIC at 0.00625:1.25 ± 0.612, 0.0125:2.5 ± 0.812, and 0.0125:2.5 ± 0.112 mg/mL (Ag:Secn). Ag-Secn-NHE-based- probiotic show minimum fungicidal concentration (MFC) at range from 2.5 to 20 mg/mL, wherever free Ag-Secn-NHE show MFC range from 5 to >20 mg/mL. Additionally, Ag-Secn-NHE-based probiotics have 75% inhibition of biofilm formation against C. auris and 60% inhibition of biofilm formation against both Cryptococcus neoformans and C. albicans in comparison with free Ag-Secn-NHE. Time-kill curves showed that the antifungal effect of Ag-Secn-NHE-based probiotics was fungistatic at 2MIC value after 4 h and after 16 h for Ag-Secn-NHE. TEM photographs showed that C. auris cells treated with Ag-Secn-NHE-based probiotic formula revealed severe deformations and distored ultrastructural changes. furthermore, results indicated that the Gamma radiation up to 15 kGy increases production of Ag-Secn-NHE in comparison with non-irradiated one.