Preparation, Characterization, and Formulation Optimization of Ionic-Liquid-in-Water Nanoemulsions toward Systemic Delivery of Amphotericin B

Amphotericin B (AmB) is an antifungal agent that poses a challenge for intravenous drug delivery due to its hydrophobicity and severe side effects that are attributed to the self-aggregation of AmB in aqueous solution. To overcome this problem, we have rationally designed an ionic-liquid-in-water nanoemulsion drug delivery system that harnesses the unique properties of ionic liquids. The complex drug AmB serves as a model pharmaceutical agent to demonstrate the robustness of ionic-liquid-in-water nanoemulsions. High concentrations of AmB were solubilized in a new hydrophobic dicholinium-based ionic liquid. The absorption spectrum of AmB in an ionic liquid mixture and prepared nanoemulsion indicates AmB solubilization in the monomeric form. The hydrophobic ionic liquid exhibits high in vivo biocompatibility with zebrafish. The hemolytic activity of the AmB nanoemulsion was negligible, yet it maintained antifungal activity against Candida albicans. The preliminary results presented in this Communication indicate that ionic-liquid-in-water nanoemulsions may allow for the delivery of a variety of pharmaceuticals intravenously, broadening the scope of ionic liquids in the pharmaceutical sciences.