Encapsulation of Flucytosine into nanoliposomes for enhanced antifungal activity against Candida glabrata and Candida albicans.

Flucytosine (FC) is currently used as an antifungal drug for the treatment of infectious diseases. However, due to the development of drug resistance, the monotherapy of FC is limited. Recently, nanoliposomes have been studied as promising approaches to overcome microbial resistance. In this study, we encapsulate FC in the nanoliposomes and investigate their physicochemical properties as well as antifungal activities against Candida glabrata and Candida albicans in-vitro. Various liposomal formulations of FC were prepared based on the modified freeze-drying of a monophase solution method. The nanoliposomes were characterized in terms of size, zeta potential, transmission electron microscopy image, encapsulation efficiency, stability, release, crystallography, and cytotoxicity. Also, the minimum inhibitory concentration and minimum fungicidal concentration were determined against C. glabrata and C. albicans. The size and zeta potential of the selected nanoliposomes were 147.33 ± 23.25 nm and - 31.20 ± 9.05 mV, respectively. Encapsulation efficiency was 46.7 ± 7.5% in the selected formulation. TEM results revealed that the nanoliposomes were nano-sized and spherical. Release results indicated that the nanoliposomes had a slow-release rate of FC. The fungal eradication of nanoliposomal FC was at least two times higher than that of the free drug for C. glabrata and C. albicans. Cytotoxicity studies demonstrated no significant toxicity at effective concentrations of nanoliposomal FC. The stability of the nano-formulation was temperature-dependent, and the refrigerator showed the best condition for long-term storage. Nanoliposomal FC prepared using the modified freeze-drying of a monophase solution method seems promising and may be used to overcome the fungal resistance relative to FC.