Abstract
BACKGROUND: Candidiasis is humans' most common oral fungal infection and is a major opportunistic fungal infection with significant morbidity and mortality, particularly in immunocompromised patients, highlighting its clinical importance worldwide. This study investigated the antifungal effect of nystatin, fluconazole, cinnamaldehyde, and nano-cinnamaldehyde on candidiasis. METHODS: In this in vitro study, nano-cinnamaldehyde formulations were prepared using span60, tween60, and cholesterol for fabrication of noisome vesicles by the ethanol injection technique. The optimum formulation (cinnosome 2) was prepared with 100 mg Span 60, 100 mg Tween 60, and 50 mg cholesterol with 5 ml of ethanol. The size and particle dispersion index (PDI) of nanoparticles were measured using Dynamic Light Scattering technique, the zeta potential was measured using Zetasizer Nano ZS, and the amount of nano-cinnamaldehyde release was measured using dialysis by USP2 dissolution device. Twenty Candida species isolates, including C. albicans, Pichia kudriavzevii, Nakaseomyces glabratus, and C. tropicalis, were obtained from clinical samples, cultured in malt extract agar medium, and fungal suspensions were prepared in RPMI medium. For antifungal evaluation, the broth microdilution test was performed, and the MIC was read after 24 h. Differences between groups were determined by Mann-Whitney and Kruskal-Wallis tests at a significance level of 0.05 via GraphPad Prism 6 and SPSS 22 software. RESULTS: Among the five niosomal formulations, the optimal nanoparticle showed a mean size of 228.75 ± 2.38 nm, PDI of 0.24 ± 0.01, zeta potential of -10.87 ± 1.09 mV, and encapsulation efficiency (EE%) of 66.71 ± 3.93%. The size of the nanoparticles varied from 137 to 297 nm among the formulations, and the particle size increased significantly with the amount of cholesterol. Nystatin, fluconazole and nano-cinnamaldehyde showed the best antifungal property with the lowest geometric mean (GM), 0.177 µg/mL, 0. 308 µg/mL and 0.554 µg/mL, respectively, followed by cinnamaldehyde (2.732 µg/mL) and carrier (2.828 µg/mL). CONCLUSIONS: According to the MIC(50) and MIC(90) values, it was found that nystatin, fluconazole, nano-cinnamaldehyde, cinnamaldehyde and carrier have the highest to the lowest antifungal property, respectively. Findings revealed that nano-cinnamaldehyde exhibited excellent antifungal activity against more than 65% of Candida isolates, indicating its promise as a potent alternative for managing oral candidiasis. CLINICAL TRIAL NUMBER: Not applicable.