Antifungal Activity of Amphotericin B Conjugated to Nanosized Magnetite in the Treatment of Paracoccidioidomycosis.
This study reports on in vitro and in vivo tests that sought to assess the antifungal activity of a newly developed magnetic carrier system comprising amphotericin B loaded onto the surface of pre-coated (with a double-layer of lauric acid) magnetite nanoparticles. The in vitro tests compared two drugs; i.e., this newly developed form and free amphotericin B. We found that this nanocomplex exhibited antifungal activity without cytotoxicity to human urinary cells and with low cytotoxicity to peritoneal macrophages. We also evaluated the efficacy of the nanocomplex in experimental paracoccidioidomycosis. BALB/c mice were intratracheally infected with Paracoccidioides brasiliensis and treated with the compound for 30 or 60 days beginning the day after infection. The newly developed amphotericin B coupled with magnetic nanoparticles was effective against experimental paracoccidioidomycosis, and it did not induce clinical, biochemical or histopathological alterations. The nanocomplex also did not induce genotoxic effects in bone marrow cells. Therefore, it is reasonable to believe that amphotericin B coupled to magnetic nanoparticles and stabilized with bilayer lauric acid is a promising nanotool for the treatment of the experimental paracoccidioidomycosis because it exhibited antifungal activity that was similar to that of free amphotericin B, did not induce adverse effects in therapeutic doses and allowed for a reduction in the number of applications.
Universidade de Brasília, Instituto de Ciências Biológicas, Departamento de Genética e Morfologia, Brasília, Distrito Federal, Brazil.
Camila Arruda
CA
Saldanha
Universidade de Brasília, Instituto de Ciências Biológicas, Departamento de Genética e Morfologia, Brasília, Distrito Federal, Brazil.
Mônica Pereira
MP
Garcia
Universidade de Brasília, Instituto de Ciências Biológicas, Departamento de Genética e Morfologia, Brasília, Distrito Federal, Brazil.
Diego Cesar
DC
Iocca
Universidade Estadual de Goiás, Unidade de Ciências Exatas e Tecnologia, Anápolis, Goiás, Brazil.
Luciana Guilherme
LG
Rebelo
Universidade de Brasília, Instituto de Ciências Biológicas, Departamento de Biologia Celular, Brasília, Distrito Federal, Brazil.
Ana Camila Oliveira
AC
Souza
Universidade de Brasília, Instituto de Ciências Biológicas, Departamento de Biologia Celular, Brasília, Distrito Federal, Brazil.
Anamélia Lorenzetti
AL
Bocca
Universidade de Brasília, Instituto de Ciências Biológicas, Departamento de Genética e Morfologia, Brasília, Distrito Federal, Brazil.
Maria de Fátima Menezes
Mde F
Almeida Santos
Universidade de Brasília, Instituto de Física, Núcleo de Física Aplicada, Brasília, Distrito Federal, Brazil.
Paulo Cesar
PC
Morais
Universidade de Brasília, Instituto de Ciências Biológicas, Departamento de Genética e Morfologia, Brasília, Distrito Federal, Brazil.
Ricardo Bentes
RB
Azevedo
D000410:Alanine Transaminase / Q000097:blood; D000666:Amphotericin B / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D003404:Creatinine / Q000097:blood; D004337:Drug Carriers; D005260:Female; D052203:Ferrosoferric Oxide / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D010228:Paracoccidioides; D010229:Paracoccidioidomycosis / Q000188:drug therapy*; D014508:Urea / Q000097:blood
D000935:Antifungal Agents; D004337:Drug Carriers; D000666:Amphotericin B; D014508:Urea; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D052203:Ferrosoferric Oxide