Antifungal activity of silver nanoparticles synthesized by iturin against Candida albicans in vitro and in vivo

Candida albicans (C. albicans) is a fungal pathogen that is difficult to cure clinically due to lack of effective antifungal agents with low toxicity. In this study, iturin, a cyclic peptide having wide antifungal spectrum, was used to synthesize nanosilver particles (AgNPs), and a complex of iturin-AgNPs was formed. The antifungal activity of iturin-AgNPs against C. albicans and its mechanisms were tested in vitro. Iturin-AgNPs were also loaded in chitosan (CS) composite dressing and applied to skin wound healing in mice. As results, iturin-AgNPs showed excellent antifungal activity with the minimum inhibitory concentrations (MIC) of 1.25, 2.5, and 5 μg/mL at C. albicans concentrations of 1×10⁵, 1×10⁶, and 1×10⁷ CFU/mL, respectively. The MIC value still kept at 2.5 μg/mL against C. albicans (10⁵ CFU/mL) after 15 regeneration, showing less induction of drug resistance to the pathogenic fungus. The antifungal mechanisms of iturin-AgNPs against C. albicans were identified as the increase of membrane permeability, damage of cell membrane integrity, and leakage of cellular protein and nucleic acids. No toxicity was found for iturin-AgNPs to HaCaT cells at concentrations of lower than 10 μg/mL. In wound healing application, iturin-AgNP CS composite dressing significantly accelerated the healing of C. albicans infected skin wounds at the early 10 days. In conclusion, iturin-AgNPs were developed as an efficient antifungal agent against C. albicans in vitro and in vivo and showed potential application in wound healing promotion.