Unleashing Fungicidal Forces: Exploring the Synergistic Power of Amphotericin B-Loaded Nanoparticles and Monoclonal...

Area of Science:

• Nanotechnology in Medicine
• Mycology
• Immunology

Background:

• Fungal infections cause significant mortality annually.
• Antifungal resistance and drug challenges limit current treatments.
• Novel therapeutic strategies are crucial for combating invasive fungal diseases.

Purpose of the Study:

• To investigate Amphotericin B (AmB) loaded polymeric nanoparticles (AmB-NPs) as a potential antifungal agent.
• To evaluate the synergistic effect of AmB-NPs combined with murine monoclonal antibodies (mAbs) CC5 and DD11.
• To assess the safety and efficacy of this combination therapy against pathogenic fungi.

Main Methods:

• AmB-NPs were prepared using nanoprecipitation with polycaprolactone (PCL) and poly(D,L-lactide) (PLA) polymers.
• Physicochemical properties and in vitro biological performance of AmB-NPs were characterized.
• Cytotoxicity assays on mammalian cells (BHK, THP-1) and antifungal activity against *C. albicans*, *C. neoformans*, and *H. capsulatum* were performed.

Main Results:

• AmB-NPs exhibited no cytotoxicity towards mammalian cells.
• AmB-NPs demonstrated significant cytotoxic effects against tested fungal species with a minimum inhibitory concentration (MIC) up to 0.031 µg/mL.
• The combination of AmB-NPs with mAbs resulted in a 2-4 fold increase in antifungal activity, indicating a synergistic effect.

Conclusions:

• AmB-NPs are a safe and effective antifungal agent against key pathogenic fungi.
• The combination of AmB-NPs with specific mAbs significantly enhances antifungal potency.
• This combination therapy represents a promising, potentially less toxic alternative to current antifungal treatments for invasive fungal infections.