Antifungal Effect of Liposomal α-Bisabolol and When Associated with Fluconazole

Abstract

Fungal pathologies caused by the genus Candida have increased in recent years due to the involvement of immunosuppressed people and the advance of resistance mechanisms acquired by these microorganisms. Liposomes are nanovesicles with lipid bilayers in which they store compounds. α-Bisabolol is a sesquiterpene with proven biological activities, and in this work it was tested alone in liposomes and in association with Fluconazole in vitro to evaluate the antifungal potential, Fluconazole optimization, and virulence inhibitory effect in vitro. Antifungal assays were performed against standard strains of Candida albicans, Candida tropicalis, and Candida krusei by microdilution to identify the IC50 values and to obtain the cell viability. The Minimum Fungicidal Concentration (MFC) was performed by subculturing on the solid medium, and at their subinhibitory concentration (Matrix Concentration (MC): 16,384 µg/mL) (MC/16), the compounds, both isolated and liposomal, were associated with fluconazole in order to verify the inhibitory effect of this junction. Tests to ascertain changes in morphology were performed in microculture chambers according to MC concentrations. Liposomes were characterized from the vesicle size, polydispersity index, average Zeta potential, and scanning electron microscopy. The IC50 value of the liposomal bisabolol associated with fluconazole (FCZ) was 2.5 µg/mL against all strains tested, revealing a potentiating effect. Liposomal bisabolol was able to potentiate the effect of fluconazole against the CA and CT strains by reducing its concentration and completely inhibiting fungal growth. α-Bisabolol in liposomal form inhibited the morphological transition in all strains tested at a concentration of MC/8. The liposomes were homogeneous, with vesicles with diameters of 203.8 nm for the liposomal bisabolol and a surface charge potential of −34.2 mV, conferring stability to the nanosystem. Through scanning microscopy, the spherical shapes of the vesicles were observed.

Keywords

• liposomes
• <i>Candida</i>
• fluconazole
• dimorphism
• nanotechnology