Synthesis, characterization and antifungal activity of a novel formulated nanocomposite containing Indolicidin and Graphene oxide against disseminated candidiasis

Candidiasis is one of the most opportunistic fungal infections in immunocompromised patients. The emergence of multidrug-resistant Candida species necessitates the development of novel antifungal agents. Seeking to the discovery of natural antifungal agents, this study aimed to synthesize a novel formulated nanocomposite containing Indolicidin (IN), antimicrobial peptide, and Graphene oxide (GO), kind of nanomaterial, against Candida growth using in vitro and in vivo experiments for the first time.The formulated nanocomposite (GO-IN) synthetized and was characterized using scanning electron microscopy, X-ray power diffraction, and fourier transform infrared method analysis. The in vitro antifungal activity of fluconazole (FLU), GO, IN, and GO-IN was determined against Candida albicans (C. albicans) compared to control groups, cell cytotoxicity assay on human intestinal epithelial cells (IEP) and hemolytic activities were performed. Moreover, in vivo experiments of nanocomposite were assessed in BALB/c mice.Our results showed that nanocomposite had the highest inhibitory effect against C. albicans (MIC 3.12μg/mL) compared with flu (MIC 4μg/mL), IN (MIC 12.5μg/mL), and GO (MIC 6.25μg/mL). Viability of human intestinal cell line at the MIC concentration (3.12μg/mL) of nanocomposite (GO-IN) was detected as 60% (P<0.05). The results of hemolytic activity showed that nanocomposite cause 2.73% of red blood cell membrane damage. For in vivo experiments, infected mice were successfully treated with GO-IN once a day within 7 days. GO-IN treated group eliminated the Candida infection in the spleen and liver of BALB/c mice (P=0.001) similar to fluconazole. There was no significant difference in histological manifestations between flu and GO-IN groups.This study suggests that synergistic combination of GO and IN provide a new option, representing a potential therapeutic efficiency against disseminated candidiasis in an animal model as well as might be used as adjunct therapy in the management of candidiasis. However, further investigation is needed to evaluate the efficacy of the nanocomposite.