Biocompatible ionic liquid-based formulations for topical delivery of ε-poly-l-lysine to combat subcutaneous fungal infections

Abstract

The skin is a critical barrier protecting internal organs from external threats, including pathogens, while also regulating body temperature. However, when pathogens invade this barrier, the integrity of the skin can be disturbed, leading to infection and disease. Fungal infections are increasing, as is fungal resistance to existing drugs, posing significant threats to public health. Here, we developed an antifungal polypeptide-based formulation for topical treatment of subcutaneous fungal infections by incorporating ε-poly-L-lysine (EPL), which has antifungal activity, with recently developed ionic liquid-in-oil formulations (IL/Os). Our results indicate that the IL/Os showed efficacy in compromising the integrity of the stratum corneum in a mouse skin model and prevented the electrostatic interaction of EPL with the SC surface. They allow the EPL to penetrate the skin, and prevent it aggregating, thus enabling it to reach the infecting fungus. EPL-loaded IL/Os demonstrated strong activity against Trichoderma viride (phylum Ascomycota) growing beneath skin. After storage at 25 °C for 28 days, EPL-loaded IL/Os retained antifungal activity similar to that of freshly prepared samples. These findings highlight the potential of EPL-loaded IL/Os for application in topical antifungal treatments.