Liposomal Myr-B, a Chionodracine-derived peptide, enhances antifungal activity >10-fold against Candida albicans and reduces biofilm

Systemic fungal infections and biofilm-associated infections pose a critical threat, exacerbated by multidrug resistance. Traditional antifungals often fall short, necessitating novel strategies. Antimicrobial peptides (AMPs) like Chionodracine are promising due to their broad-spectrum activity, but their therapeutic potential is hampered by poor in vivo stability and aggregation. Developing effective delivery systems is crucial to overcome these limitations and unlock their clinical utility against challenging pathogens such as Candida auris, a critical priority pathogen.

Researchers investigated the lipopeptide Myr-B, a myristoylated derivative of Chionodracine, for its encapsulation in liposomes. They explored thin-film hydration and lipid-cake preparation methods, selecting two optimal formulations based on dimyristoylphosphatidylcholine and cholesterol/cholesteryl-hemisuccinate. Physico-chemical characterization was integrated with molecular dynamics simulations. The antifungal activity of Myr-B-loaded liposomes was assessed by determining minimum inhibitory concentrations (MICs) against Candida albicans and Candida tropicalis, and LIVE/DEAD imaging was used to evaluate biofilm formation. Safety was evaluated via haemolysis assays, cytotoxicity against human fibroblasts, and in vivo tolerability in Galleria mellonella.

The lipid-cake method proved optimal, yielding monodisperse, stable liposomes with high encapsulation efficiency. Encapsulation in both selected liposome formulations markedly enhanced antifungal activity. > Liposomal Myr-B lowered minimum inhibitory concentrations (MICs) by more than ten-fold against Candida albicans and approximately four-fold against Candida tropicalis compared to free Myr-B.