الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
This study aimed to screen various bacterial species recovered from different soil samples for their potential antifungal activities against C. albicans ATCC 10231 and A. niger clinical isolate followed by purification, characterization and optimized production of the respective culture metabolite(s) showing promising antifungal activities also the formulation of these antifungal agents into suitable dosage form to be tested in vitro, in vivo, and ex vivo. Initially, we screened soil bacterial isolates for the capability of producing metabolites with antifungal activities via the cross streak, dual culture, and agar well diffusion methods. isolate, coded F1, showed significant antifungal activities against C. albicans ATCC 10231 and A. niger clinical isolate.
Soil bacterium identified as Bacillus toyonensis (OQ071612) using morphology, biochemical tests, and 16S rRNA sequencing. This bacterium is known for its beneficial bioactive compounds, including antifungal secondary metabolites. Previous studies reported its antifungal activity against various fungal pathogens and antimicrobial properties. The antifungal metabolite was identified as 6-methoxy-1H-indole-2-carboxylic acid (MICA) using spectral analysis e.g. UV, 2D-NMR and LC-MS harboring the well-known antifungal and antimicrobial moiety, indole carboxylic acid. This represents the first report of this specific metabolite production by B. toyonensis OQ071612.
MICA was secreted extracellularly by B. toyonensis (OQ071612) with a high yield (0.28 mg/mL) exhibiting significant fungicidal activity against Candida albicans and Aspergillus niger. Response surface methodology (RSM) was employed to optimize the production of the antifungal metabolite. Starch, peptone, temperature, and pH were identified as significant factors influencing its yield. Under optimized conditions (starch, peptone, 37°C, pH 7), a remarkable 3.49-fold increase in production was achieved compared to unoptimized conditions. This substantial improvement paves the way for potential large-scale production and application in antifungal therapy.
This study also successfully developed and optimized nanosponges loaded with the potent antifungal compound ODHP (extracted and purified in our previous lab study) & MICA for topical application. Employing a Box-Behnken design, the researchers achieved optimal particle size, distribution, and drug entrapment within the nanosponges. characterization revealed a homogenous spherical morphology with suitable stability and monodispersity. Encapsulated within a carbopol 940 hydrogel base, the ODHP&MICA-nanosponge formulation (ODHP-NS-HG &MICA-NS-HG) exhibited excellent spreadability, high drug retention, and favorable release kinetics. In vitro studies demonstrated superior antifungal activity against C. albicans compared to the control, while maintaining acceptable cytotoxicity against mammalian cells.
Notably, in vivo studies in a rat model revealed enhanced survival rates, increased dermal collagen deposition, and accelerated wound healing in ODHP-NS-HG &MICA-NS-HG treated groups. Furthermore, ELISA analysis indicated suppression of inflammatory markers and upregulation of a pro-angiogenic factor, suggesting the formulation’s ability to combat inflammation and promote tissue repair. Overall, this study presents a promising ODHP-NS-HG &MICA-NS-HG with potent antifungal activity, enhanced wound healing potential, and minimal side effects, paving the way for its future application in topical fungal infections.