Biofabricated Silver Nanoparticles Synergistically Activate Amphotericin B Against Mature Biofilm Forms of Candida Albicans

Abstract

Background: Biofilm formation by Candida albicans is a significant clinical challenge. Fungal biofilms are resistant to most of the currently available antifungal agents. Amphotericin-B (AmB) is an antifungal agent used for the treatment of systematic fungal infections but it is well known for its toxicities and side-effects. Novel approaches are needed to treat these infections that can reduce its toxicities. Objectives: Current study aims to evaluate the efficacy of silver nanoparticles (SNPs) alone and in combination with AmB against growth and biofilm formation in C. albicans. Methods: Combinations of SNP-AmB were tested against planktonic growth and biofilm formation in vitro. Micro broth dilution method was used to study planktonic growth and biofilm formation. The fractional inhibitory concentration indices (FICI) were calculated by using a checkerboard format. Biofilm formation was analyzed by using XTT-metabolic assay. Results: MIC of AmB for developing biofilm was lowered by 16 fold in combination with SNPs. The calculated fractional inhibitory concentration indices were 0.1875 suggesting that this interaction is synergistic. Similarly, the mature biofilms were significantly prevented by SNPs-AmB combination. This interaction was synergistic. Furthermore, interaction between SNPs and AmB against planktonic growth was additive. Hemolytic activity assay was carried out on these drugs and combinations. Drug required for inhibition alone as well as in combination did not exhibit hemolytic activity. Conclusion: The combinations with SNPs lead to decreases in the dosage of AmB required for anti-Candida activity. SNPs-AmB combination could be an effective strategy against biofilm formed by C. albicans.