Evaluation of the physicochemical preoperties of Flocytosine nanoliposomes and their in vitro antifungal effects on candida albicans

Abstract

Flucytosine has been approved as an antifungal drug for the treatment of systemic candidal infections, cryptococcal meningitis, fungal pneumonia, sepsis, candidal or cryptococcal urinary tract infections, and chromomycosis. Its off-label use is in the treatment of pediatric endocarditis caused by Aspergillus. Objective: The main purpose of this study was to prepare flucytosine nanoliposomes and to investigate their physicochemical properties and antifungal effects against Candida albicans and evaluate their toxicity on cervical cells via in vitro method. Flucytosine liposome formulations were prepared by mono-phase solution lyophilization. Liposomes were evaluated for particle size, zeta potential, encapsulation efficiency, cytotoxicity, stability, release, crystallography, and calorimetric properties. Also, the minimum lethal and inhibitory resistance of both free forms and flucytosine nanoliposomes on Candida albicans yeast was studied by the micro broth dilution method. Results: Flucytosine-containing nano-lipomal formulations were successfully produced. The results of physicochemical evaluations showed that nano-liposomes had an encapsulation efficiency of 51%. Cytotoxicity studies showed that nano-formulated flucytosine did not have significant toxicity at effective concentrations and finally the stability results showed that the stability of nano-formulation is temperature-dependent and refrigerator temperature has the best conditions for long-term storage. Examination of the inhibitory and lethal concentrations of flucytosine against yeasts showed that encapsulation doubled its effectiveness. Release studies showed that nano-formulated drug had slow release rate of flucytosine Conclusion: Using the modified mono-phase lyophilization method, nano-liposomes containing flucytosine can produce good encapsulation efficiencies as well as enhanced antifungal effect relative to the drug solution. Nanoliposome did not have significant toxicity at effective concentrations and had slow release rate of drug than drug sloution