Preparation of Flucytosine loaded liposomes and evaluation of the in vitro antifungal effect on Candida glabrata compared to the drug solution

Abstract

Introduction: Flucytosine has attained approval as an adjunct antifungal agent in the treatment of systemic Candida or Cryptococcus infections. Off-label, flucytosine is utilized in treating pediatric endocarditis caused by Aspergillus spp Flucytosine is an antimetabolite compound absorbed into fungal cells via cytosine permease. Within the fungal cell, flucytosine gets converted to 5-fluorouracil, which interferes with fungal RNA biosynthesis Aim: The main objective of this investigation was to encapsulate fluocytosine in the nanoliposomal formulation to study their antifungal activities in vitro against Candida glabrata yeast. Methods: Different liposomal formulations of 5-FC were prepared based on the modified freeze-drying of a monophase solution. The liposomes were characterized in terms of Size, Zeta potential, Polydispersity index, Tem and Encapsulation efficiency. Also, MICs of free and nanoliposomal 5-FC against Candida glabrata yeast were investigated by the standard broth macro-dilution method. Results: The size and zeta potential of the prepared liposomes were from 178.7 to 523.8 nm, and -65.55 to -31.35mV, respectively. Encapsulation efficiency was 41.31% in the best formulation. Also, TEM results showed that the liposomes were nano-sized and spherical in shape. Most importantly, Fungal eradication by liposomal 5-FC (MIC=0.058 µg/ml) was about 2-fold higher than free 5-FC (MIC = 0.11 μg / ml) for Candida glabrata. Conclusions: Nanoliposomal 5-FU prepared using the modified freeze-drying of a monophase solution method could increase the entrapment efficiency as well as the antifungal effect of the antibiotic compared to the drug solution