Abstract
Amphotericin B (AmB) is a potent antifungal successfully used intravenously to treat visceral leishmaniasis but depending on the Leishmania infecting species, it is not always recommended against cutaneous leishmaniasis (CL). To address the need for alternative topical treatments of CL, the aim of this study was to elaborate and characterize an AmB gel. The physicochemical properties, stability, rheology and in vivo tolerance were assayed. Release and permeation studies were performed on nylon membranes and human skin, respectively. Toxicity was evaluated in macrophage and keratinocyte cell lines, and the activity against promastigotes and intracellular amastigotes of Leishmania infantum was studied. The AmB gel remained stable for a period of two months, with optimal properties for topical use and no apparent toxic effect on the cell lines. High amounts of AmB were found in damaged and non-damaged skin (1230.10 ± 331.52 and 2484.57 ± 439.12 µg/g/cm2, respectively) and they were above the IC50 of AmB for amastigotes. Although there were no differences in the in vitro anti-leishmanial activity between the AmB solution and gel, the formulation resulted in a higher amount of AmB being retained in the skin, and is therefore a candidate for further studies of in vivo efficacy.
Highlights
Leishmaniasis are a group of diseases caused by species of Leishmania protozoan parasites and transmitted by the bite of Phlebotomine sand flies
Due to the safe usage of other Amphotericin B (AmB) formulations that has been previously reported in healthy volunteers [55], and prompted by the study of López et al (2018), who concluded that their 3% AmB cream tested in patients with uncomplicated Cutaneous leishmaniasis (CL) needed reformulation of either the vehicle or concentration [56], we propose Sepigel 305® as a suitable vehicle for 0.1% AmB for topical treatment
The development of a topical treatment for CL is desirable, as painful intralesional treatments are widely rejected by patients
Summary
Leishmaniasis are a group of diseases caused by species of Leishmania protozoan parasites and transmitted by the bite of Phlebotomine sand flies. There are three main forms of the disease and the manifestations depend on the infecting species, the immunological system of the patient and the area of inoculation [2,3]. In the Mediterranean area, Leishmania infantum is the main causal agent of VL and CL [5], and in Spain, L. infantum is the responsible for the endemic CL cases [6,7]. Pentavalent antimonials (meglumine antimoniate and sodium stibogluconate) are administered intravenously or by painful intralesional injections which are frequently discontinued by patients, which promotes resistances [10]
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