Topical Amphotericin B Semisolid Dosage Form for Cutaneous Leishmaniasis: Physicochemical Characterization, Ex Vivo Skin Permeation and Biological Activity

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.

Preclinical safety evaluation of amphotericin A21: A novel antifungal

“…The use of antifungals for local use is also a necessity since, in addition to cutaneous fungal infections, there are diseases such as leishmaniasis where dermal application is also effective 34,35 . Some recent research has focused on developing new topical formulations of amphotericin B 36‐38 ; however, due to its lipid solubility, there is a possibility it can still be absorbed and produce systemic toxic effects. AmB‐A21, therefore, might also be usefully employed for cutaneous fungal infections at low doses.…”

Semisolid Dosage

“…Berenguer and coworkers present results on a ''Topical Amphotericin B (AmB) Semisolid Dosage Form for Cutaneous Leishmaniasis: Physicochemical Characterization, Ex-Vivo Skin Permeation and Biological Activity" [6]. The study describes an AmB gel that proved to be stable for 60 days at 4 • C and showed characteristics that made it favorable for cutaneous application.…”

Pharmacokinetics and pharmacodynamics in the treatment of cutaneous leishmaniasis – challenges and opportunities

“…Extraction of the skin as a whole or distinct layers allows the evaluation of drug disposition profiles a methodology frequently used to compare drug distribution profiles of distinct formulations. 33,86 Besides the drugs highlighted above, topical formulations incorporating natural extracts have also been exploredsome displaying promising results in in vivo CL models. [87][88][89] It is important to note that commonly encountered problems such as (i) batch-to-batch variability of the extract, which may contribute to formulation and instability issues, (ii) availability of the plant material in sufficient quantities, and (iii) difficulties to identify the antileishmanial active molecule(s) compromise translatability and downstream development processes.…”