Topical Amphotericin B Semisolid Dosage Form for Cutaneous Leishmaniasis: Physicochemical Characterization, Ex Vivo Skin Permeation and Biological Activity
Diana Berenguer,
Maria Magdalena Alcover,
Marcella Sessa,
Lyda Halbaut,
Carme Guillén,
Antoni Boix-Montañés,
Roser Fisa,
Ana Cristina Calpena-Campmany,
Cristina Riera,
Lilian Sosa
Affiliations
Diana Berenguer
Department of Biology, Health and Environment, Laboratory of Parasitology, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
Maria Magdalena Alcover
Department of Biology, Health and Environment, Laboratory of Parasitology, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
Marcella Sessa
Department of Pharmaceutical Technology and Physicochemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
Lyda Halbaut
Department of Pharmaceutical Technology and Physicochemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
Carme Guillén
Department of Biology, Health and Environment, Laboratory of Parasitology, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
Antoni Boix-Montañés
Department of Pharmaceutical Technology and Physicochemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
Roser Fisa
Department of Biology, Health and Environment, Laboratory of Parasitology, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
Ana Cristina Calpena-Campmany
Department of Pharmaceutical Technology and Physicochemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
Cristina Riera
Department of Biology, Health and Environment, Laboratory of Parasitology, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
Lilian Sosa
Department of Pharmaceutical Technology and Physicochemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
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.