Polyene macrolide antibiotic nanoemulsion: a proposal for the treatment of cutaneous leishmaniasis

Abstract

Leishmaniasis is a neglected tropical disease that requires timely and inexpensive treatment. For this purpose, a nanoemulsion with a polyene macrolide antibiotic, or amphotericin B (NE-AmB), was developed. This study quantified the amount of drug permeated and retained in intact and lacerated human skin, simulating cutaneous leishmaniasis (CL) processes. Toxicity in macrophage and keratinocyte cell lines, activity against promastigotes and amastigotes of Leishmania tropica, in vivo irritant activity, and histological evidence was evaluated. Results. The amount of drug retained in intact and damaged skin was 750.18 ± 5.43 and 567.97 ± 8.64 µg/g/cm2, respectively. There was no permeation. No apparent toxic effect was observed in HaCaT cell lines. The IC50 of NE-AmB found for promastigotes and amastigotes was 0.26 ± 0.09 and 0.37 ± 0.05 µg/mL, respectively. NE without AmB did show antiparasitic activity. The formulation showed lower IC50 values on both parasite stages than the AmB solution. There was no skin irritation, and histology showed skin improvement with treatment. We suggest that this NE-AmB may be a candidate for in vivo studies in CL patients. Keywords. Leishmaniasis, Amphotericin B, ex vivo permeation studies, in vitro cytotoxicity, in vitro leishmanicidal activity, Draize test, histology.