RESUMEN

Fungal resistance is the major problem related to fluconazole treatments. This study aims to develop innovative lipid core nanocapsules and nanostructured lipid carriers containing fluconazole, to study in vitro antifungal activity and to assess the possibility of resistance reversion in Candida albicans, C. glabrata, C. krusei, and C. tropicalis isolates. The action mechanism of nanoparticles was investigated through efflux pumps and scanning electron microscopy studies. The lipid core nanocapsules and nanostructured lipid carriers were prepared by interfacial deposition of preformed polymer and high-pressure homogenization methods, respectively. Both nanostructures presented sizes below 250 nm, SPAN < 1.6, negative zeta potential, pH slightly acid, high drug content and controlled drug release. The nanostructured lipid carriers were unable to reverse the fungal resistance. Lipid core nanoparticles displayed advantages such as a reduction in the effective dose of fluconazole and resistance reversion in all isolates tested - with multiple mechanisms of resistance. The main role of the supramolecular structure and the composition of the nanoparticles on antifungal mechanisms of action were discussed. The results achieved through this study have an impact on clinical therapy, with a potential application in the treatment of fungal infections caused by resistant isolates of Candida spp.

Asunto(s)

Antifúngicos/farmacología , Candida/efectos de los fármacos , Preparaciones de Acción Retardada/química , Farmacorresistencia Fúngica/efectos de los fármacos , Fluconazol/farmacología , Proteínas Fúngicas/antagonistas & inhibidores , Nanopartículas/química , Transportadoras de Casetes de Unión a ATP/antagonistas & inhibidores , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Candida/genética , Candida/crecimiento & desarrollo , Candida/metabolismo , Candida albicans/efectos de los fármacos , Candida albicans/genética , Candida albicans/crecimiento & desarrollo , Candida albicans/metabolismo , Candida glabrata/efectos de los fármacos , Candida glabrata/genética , Candida glabrata/crecimiento & desarrollo , Candida glabrata/metabolismo , Candida tropicalis/efectos de los fármacos , Candida tropicalis/genética , Candida tropicalis/crecimiento & desarrollo , Candida tropicalis/metabolismo , Caprilatos/química , Composición de Medicamentos/métodos , Farmacorresistencia Fúngica/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Expresión Génica , Genes MDR/efectos de los fármacos , Hexosas/química , Concentración de Iones de Hidrógeno , Pruebas de Sensibilidad Microbiana , Nanopartículas/ultraestructura , Palmitatos/química , Tamaño de la Partícula , Triglicéridos/química , Verapamilo/farmacología