Development, characterization, and in vitro biological performance of fluconazole-loaded microemulsions for the topical treatment of cutaneous leishmaniasis.

Marcela Brito Oliveira,Márcia Graminha,Mercedes González,Giovana Calixto,Hugo Cerecetto,Marlus Chorilli

doi:10.1155/2015/396894

Abstract

Cutaneous leishmaniasis (CL) is a resistant form of leishmaniasis that is caused by a parasite belonging to the genus Leishmania. FLU-loaded microemulsions (MEs) were developed by phase diagram for topical administration of fluconazole (FLU) as prominent alternative to combat CL. Three MEs called F1, F2, and F3 (F1—60% 50 M phosphate buffer at pH 7.4 (PB) as aqueous phase, 10% cholesterol (CHO) as oil phase, and 30% soy phosphatidylcholine/oil polyoxyl-60 hydrogenated castor oil/sodium oleate (3/8/6) (S) as surfactant; F2—50% PB, 10% CHO, and 40% S; F3—40% PB, 10% CHO, and 50 % S) were characterized by droplet size analysis, zeta potential analysis, X-ray diffraction, continuous flow, texture profile analysis, and in vitro bioadhesion. MEs presented pseudoplastic flow and thixotropy was dependent on surfactant concentration. Droplet size was not affected by FLU. FLU-loaded MEs improved the FLU safety profile that was evaluated using red cell haemolysis and in vitro cytotoxicity assays with J-774 mouse macrophages. FLU-unloaded MEs did not exhibit leishmanicidal activity that was performed using MTT colourimetric assays; however, FLU-loaded MEs exhibited activity. Therefore, these MEs have potential to modulate FLU action, being a promising platform for drug delivery systems to treat CL.

Highlights

IntroductionLeishmaniasis is an anthropozoonosis with natural foci that affects 12 million people worldwide, with approximately 1-2 million new cases occurring every year, and persists in tropical and subtropical regions [1]
Leishmaniasis is an anthropozoonosis with natural foci that affects 12 million people worldwide, with approximately 1-2 million new cases occurring every year, and persists in tropical and subtropical regions [1].It is caused by a parasite belonging to the genus Leishmania, in which infection is spread in wild ecotopes by the bite of the infected female sandfly (Phlebotomine) in their vertebrate hosts [2,3,4].These parasites can originate two types of diseases: visceral or cutaneous leishmaniases
liquid and transparent systems (LTS) regime was observed at low oil concentrations (10%) and low surfactant concentrations (10–30%); transparent viscous systems (TVS) regime was observed for surfactant concentrations between 20 and 65% and oil concentrations of 10 to 40%; viscous and opaque systems (VOS) regime was found in the lower central region of the diagram at low oil concentrations of 20–50% and surfactant concentrations

Summary

Introduction

Leishmaniasis is an anthropozoonosis with natural foci that affects 12 million people worldwide, with approximately 1-2 million new cases occurring every year, and persists in tropical and subtropical regions [1] It is caused by a parasite belonging to the genus Leishmania, in which infection is spread in wild ecotopes by the bite of the infected female sandfly (Phlebotomine) in their vertebrate hosts [2,3,4]. These parasites can originate two types of diseases: visceral or cutaneous leishmaniases. Amphotericin B, pentamidine isethionate, miltefosine, and paromomycin are available as alternatives therapies, but their use is limited because of toxicity or high treatment costs [6]

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