Search

This study reports on the use of surface-enhanced Raman scattering (SERS) detection and follow-up treatment of Paracoccidioides brasiliensis (Pb) infection in lung's mice. We also reports on the introduction of a new drug carrier system [nanoparticle-Amphotericin B (NP-AmB)], comprising magnetic NP surface functionalized with AmB, and its use in the treatment of infected and non-infected mice. SERS was successfully used to monitor the efficacy of the mice's treatment using the new NP-AmB, while free AmB (F-AmB), considering the current drug of choice for treatment of Pb infection, was also used and taken as reference for the treatment. We found SERS provides a robust platform to discriminate infected lung tissues from non-infected ones based on fingerprints assessed via SERS spectra and focused on the redox state of heme groups present in the collected biological material. Finally, SERS data reported in this study indicated that the new NP-AmB formulation provides similar clinical response as the F-AmB, although incorporating 40% lower content of AmB and administered in a time interval schedule (every 72 h) three times longer than F-AmB (every 24 h). Copyright © 2013 John Wiley & Sons, Ltd.

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., Author Summary Lung fungal infections are caused by pathogens inhaled as spores which convert into invasive yeast forms in the lungs. This type of infection can spread to other sites in the body through the blood and lymphatic systems, sometimes leading to ulcerations and skin lesions. The drug of choice for treatment is Amphotericin B (AmB). AmB is a typical polyene with broad-spectrum antifungal activity that encounters some use limitations because of its side effects. We developed a magnetic carrier nanocomplex comprising of amphotericin B loaded onto the surface of magnetite nanoparticles pre-coated with a double-layer of lauric acid. We evaluated this approach for its antifungal activity against Paracoccidioides brasiliensis (strain Pb18) and its cytotoxicity in mammalian cell culture. We found that this nanocomplex exhibited antifungal activity without cytotoxicity to human urinary cells and low cytotoxicity to peritoneal macrophages. In vivo, the nanocomplex did not induce genotoxic effects in bone marrow cells and was effective against experimental paracoccidioidomycosis without inducing clinical, biochemical or histopathological alterations.