Application of New Syncretic Antifungal Formulations against Candida Species Associated with Oral Cancer

Background: Human oral microbiomes constitute from diverse and multifaceted structure of microorganisms including fungi and bacteria. That complex structure is dynamic and plays important roles in human health and disease. They might influence the progress of infectious diseases like oral cancer. Some of oral mycobiota may transform to bloodstream causing severe systematic diseases and a greater risk of sickness and death up to 79% of oral cancer patients. Oral cancer isolates were detected to be more virulent compared with other studied isolates including non-cancer isolates.

Aims: The aims of this study were to investigate the in vitro effects of ZnO NPs and apple cider vinegar (ACV) independently against Iraqi isolates of Candida albicans and Candida tropicalis isolated from oral cancer patients and healthy individuals. Dual and triple combinations of ZnO NPs or/and ACV combined with fluconazole (Flu) and Amphotericin B (AmphB) were tested against Candida isolates and first applied as alternative therapies in Iraq and in some application points around the world.

Methods: The two most common types C. tropicalis (P128), (H25) and C. albicans (P111), (H10) were selected against a range of concentrations of ZnO NPs, Flu and amphB (0.01-0.06 and 0.1 µg/ml) and six concentrations of ACV (50,000-780µg/ml) using micro dilution method. The minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) for each antifungal agent and their interactions among these drugs were also detected.

Result: The oral cancer isolates were more resistance to tested antifungals and their combinations compared with non-cancer isolates. Dual and triple combinations were synergistic and showed significant reductions in fungal growth in a dose dependent matter. The triple combination of ZnO NPs and ACV with Flu or AmphB revealed notable reduction in MICs and MFCs values.

Conclusion: These concentration-dependent interactions may have critical effects that need further study in animal models of investigated species.

The dual combination of ZnO NPs and ACV had a significant similarity with triple antifungal combinations of antifungal activity against Candida tropicalis.