XI International Meeting on Paracoccidioidomycosis

XI International Meeting on Paracoccidioidomycosis

Resume:131-1

Poster (Painel)

131-1

Experimental paracoccidioidomycosis treatment using nanostructured amphotericin B in poly-lactic-co-glycolic acid (Nano-D-AMB) and AmBisome®: antifungal comparision in vivo and evaluation of cytotoxicity in vitro

Authors:

Ana Camila Oliveira Souza (UNB - Universidade de Brasília) ; Nathalia Moraes de Vasconcellos (UNB - Universidade de Brasília) ; Márcio Sousa Jerônimo (UNB - Universidade de Brasília) ; Isaque Medeiros Siqueira (UNB - Universidade de Brasília) ; André Corrêa Amaral (UFG - Universidade Federal do Goiás) ; Maria Sueli Soares Felipe (UNB - Universidade de Brasília) ; Anamélia Lorenzetti Bocca (UNB - Universidade de Brasília)

Abstract

The development of polymeric nanoparticles has produced great advances in diseases treatments, often allowing an increase in therapeutic efficacy and reduced toxicity of the drug. Several nanoformulations to existing drugs has been proposed and tested, carrying for example anti-cancer agents, hormones and antibiotics. This is the case of amphotericin B, used in the treatment of some systemic mycoses such as paracoccidioidomycosis and candidiasis, though it causes various side effects, including nephrotoxicity and kidney failure after prolonged use. The nanostructuring of amphotericin B in poly-lactic-co-glycolic acid (Nano-D-AMB) was shown to be effective in the treatment of experimental paracoccidioidomycosis, with similar antifungal capacity and decreased number of applications compared to treatment with free formulation. In this context, the objective of this study was to compare the efficacy of liposomal amphotericin B (AmBisome®) and Nano-D-AMB in the treatment of murine paracoccidioidomycosis and assess their cytotoxicity in vitro. BALB/c mice were infected with Paracoccidioides brasiliensis and after 60 days, they were treated with AmBisome® or Nano-D-AMB at a dose of 6mg/kg/day every three days. After 30 days the animals were sacrificed for quantification of colony forming units per gram of lung tissue, lung, kidneys and liver histopathology, and spleen lymphocyte proliferation. In animals treated with Nano-D-AMB or AmBisome® it was observed lower fungal burden and less lung damage compared to untreated animals, and a partial recovery of proliferative capacity, markedly reduced during the untreated disease. It was not observed morphological changes in liver and kidney nor in body weight between the experimental groups. The evaluation of cytotoxicity in peritoneal macrophages and erythrocytes showed increased viability in cells treated with Nano-D-AMB or AmBisome® compared to those treated with free amphotericin B. These results demonstrate similar therapeutic efficacy in vivo of Nano-D-AMB and AmBisome® and their lower cytotoxicity in vitro.

Keyword: Paracoccidioidomycosis, Nanoparticles, Anphotericin B, Ambisome, PLGA

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