Study of potential fluconazole-loaded microemulsions for the treatment of mucocutaneous leishmaniasis

• Grant number: 11/10595-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2011
• End date: April 30, 2013
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Marlus Chorilli
• Grantee: Marcela Brito Oliveira
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Mucocutaneous leishmaniasis is caused by infected female sandflies insects. The lesions may evolve from papules to ulcers, showing granular base and infiltrated side, which are painless and can be single or multiple. They can manifest as verrucous plaques, nodular, localized or diffuse. This is a neglected disease and investment on treatment is negligible. It can be employed in the treatment medications based on pentavalent antimony, in addition to other drugs such as pentamidine, amphotericin B, allopurinol, azithromycin, antifungals, imidazoquinolines, paromomycin and miltosine. Many of these drugs are toxic and present in injectable dosage form, which must be applied until the disappearance of skin lesions. Antifungal bis-triazoles such as fluconazole (FLU) have been used in the treatment of some species of Leishmania, because it inhibits the synthesis of specific and essential steroid for growth and viability of the parasite. The incorporation of drugs into nanostructured systems, as microemulsions, it is extremely interesting as a way to promote controlled release of active substances at the injury site, while protecting the active principle of thermal degradation or photodegradation. This work aims to develop and characterize FLU-loaded microemulsions, to perform the physical and chemical stability, to assess the in vitro release of the formulations and to carry out in vitro biological assays. The structural characterization will be performed by analysis of polarized light microscopy, X-ray scattering small angle (SAXS), droplet size analysis, rheological behavior and texture profile. In the stability study will be employed visual evaluation and determination of pH. It will be performed in vitro release assays using cellulose acetate membrane and the quantification of the antifungal agent released from microemulsions it will be conducted using the methodology validated by high performance liquid chromatography. In the in vitro biological assays, colorimetric assays will be carried out of samples to verify if the developed system allows the enhancement of the leishmanicid action of the FLU against promastigotes forms of L. amazonensis.