Owing to the high mortality and morbidity around the world due to resistant fungal infections, there is a growing interest in the potential role of natural products in curbing the fungal crawling. Considering this, our research targeted to investigate the efficacy of two Saudi propolis samples against two Candida Species (C. albicans & C. krusei). Saudi propolis samples were defatted firstly by petroleum ether yielding (P1pt. & P2pt.), then extracted with ethyl acetate yielding (P1E & P2E). The antifungal activity of the four fractions was estimated against C. albicans, the most popular infectious fungal pathogen and the multidrug resistant C. krusei.
P2E possessed the highest inhibitory activity for both C. krusei and C. albicans with inhibition zones of 37 ±0.089 & 31 ±0.073 mm and a MIC; 2.5& 4.0 mg/ml, respectively. Whilst P1E showed a strong inhibition activity only for C. krusei with inhibition zone diameter of 30±0.094 mm and a MIC equal to 60 mg/ml. GC/MS investigation for (P1E & P2E) revealed the detection of 77 compounds from different chemical classes, caffeate esters were solely present in P2E in a relatively high amount. In-silico study was conducted to predict the P2E major bioactive components possible binding affinity mechanism to three potential enzymes for the growth and survival of candida species, results revealed that many of the examined compounds had a reasonable binding affinity which could explain the significant P2E anti-candida activity. Eventually, P2E was loaded in Soluplus-based self-nanoemulsifying tablets to overcome its low aqueous solubility and oral bioavailability, the selected formula showed a significant better active agents release compared to the plain fraction (100 % and 20 %, respectively), which proves the beneficial effect of the designed nano-system.