Liposomal Amphotericin B Formulation Displaying Lipid-Modified Chitin-Binding Domains with Enhanced Antifungal...

Area of Science:

• Mycology
• Biochemistry
• Drug Delivery

Background:

• Fungal infections are a major global health concern, causing over a million deaths annually.
• Amphotericin B (AmB) is a potent antifungal but has significant side effects, leading to the development of AmBisome.
• There is a need for improved antifungal formulations with enhanced efficacy and reduced toxicity.

Purpose of the Study:

• To develop a strategy for enhancing the antifungal activity of AmBisome.
• To create a lipid-modified protein for targeted delivery to fungal cell walls.
• To evaluate the efficacy and safety of the modified AmBisome formulation.

Main Methods:

• Engineered a chitin-binding domain (LysM) from *Pteris ryukyuensis* chitinase A.
• Modified LysM with a lipid moiety (palmitoyl) via enzymatic crosslinking using microbial transglutaminase (MTG).
• Anchored the lipid-modified LysM (LysM-Pal) to AmBisome to create LysM-AmBisome.

Main Results:

• LysM-AmBisome demonstrated significantly enhanced antifungal activity against *Trichoderma viride* and *Cryptococcus neoformans*.
• The modified formulation showed negligible cytotoxicity to mammalian cells.
• The strategy effectively improved the targeting ability of the liposomal drug formulation.

Conclusions:

• Displaying cell-wall binding proteins on liposomal formulations can dramatically enhance antifungal efficacy.
• Enzymatic protein lipidation is a potent approach for upgrading lipid-based drug delivery systems.
• LysM-AmBisome represents a promising advancement in antifungal therapy.