Are hydrophilic deep eutectic solvents a potential vehicle for topical delivery of Amphotericin B against cutaneous leishmaniasis? An investigation of physicochemical properties, tolerability and antileishmanial efficacy.

Deep eutectic solvents (DES) are homogenous, low-melting mixtures that are liquid at ambient temperature. Recently, DES have attracted interest as novel alternatives to traditional solvents in cutaneous formulations. The aim of this work was to have a better understanding of whether DES could be a safe and effective vehicle for topical delivery of Amphotericin B (AmB) in Cutaneous Leishmaniasis (CL). Based on solubility data, solutions of AmB in DES were prepared and characterized in terms of rheological properties, stability, and aggregation state of AmB by circular dichroism. The tolerability of DES-AmB on the skin was investigated by combining non-invasive techniques with histological assessment; systemic toxicity was also studied. Finally, the best-tolerated formulations were selected for direct assessment of both therapeutic efficacy and toxicity in a murine model of CL. Some of the formulations, especially those based on L-carnitine, could be promising candidates for further development of effective drug formulations against CL, as they were able to show either partial antileishmanial or palliative effects in robust test conditions. However, further optimization is necessary to ensure optimal stability and efficacy of the formulations.