Enhancing Flucytosine Anticandidal Activity Using PEGylated Squalene Nanocarrier

Area of Science:

• Pharmaceutical Nanotechnology
• Antimicrobial Therapy
• Mycology

Background:

• Candida infections pose a significant global health challenge.
• Existing antifungal treatments have limitations, including emerging resistance.
• Flucytosine (5FC) shows antifungal potential but requires combination therapy for efficacy.

Purpose of the Study:

• To develop PEGylated squalene-based nanocarriers for enhanced flucytosine (5FC) monotherapy.
• To improve the efficacy of 5FC against Candida strains through nanotechnology.

Main Methods:

• Flucytosine (5FC) was loaded into PEGylated squalene micelles using ultrasound-assisted solvent evaporation.
• Nanocarrier characterization included STEM, DLS, and UV-Vis spectroscopy for drug loading.
• In vitro drug release studies and antifungal activity assays against Candida species were performed.

Main Results:

• Characterization confirmed core-shell nanocarriers with optimal dimensions and stability.
• Sustained 5FC release over 48 hours was observed, following a Fickian diffusion mechanism.
• The nanotherapeutic demonstrated enhanced in vitro antifungal activity against Candida albicans, glabrata, and parapsilosis.
• No significant increase in in vitro toxicity toward normal cells was detected.

Conclusions:

• PEGylated squalene nanocarriers effectively deliver 5FC, enhancing its monotherapy efficacy.
• This nanodelivery system represents a promising advancement for treating Candida infections.
• The approach offers improved antifungal activity with maintained safety profiles for normal cells.