Avaliação do potencial terapêutico de nanopartículas com Itraconazol por via inalatória em camundongos experimentalmente infectados com paracoccidioides brasiliensis

Abstract

Inhalation of antifungal agents has been used for the prevention and treatment of pulmonary fungal infections experimentally for some decades, although there are no commercial formulations available for this purpose and chronic use by oral or intravenous route of antifungal agents, cause side effects mainly in the gastrointestinal tract and renal function. Thus, the aim of this work was to synthesize a new nanoparticles itraconazole formulation and to evaluate the response to inhalation treatment of Swiss mice experimentally infected with Paracoccidioides brasiliensis, the etiological agent of most frequent systemic mycosis in Latin America. The animals were divided into 4 groups: Group 1 – uninfected/untreated, Group 2 – Infected/untreated, Group 3 – Infected/Oral treatment, Group 4 – Infected/inhalation treatment. Results demonstrated that is possible to synthesize a solution of itraconazole at physiological nebulisable pH, with comparable “in vitro” efficacy to the standard drug and that can be administered by inhalation in an animal model of pulmonary infection by P. brasiliensis, it is also functional, since macroscopy and microscopy results show a significant reduction in the number of granulomas in mice treated with this solution by inhalation.