Biodistribution of free and encapsulated 99mTc-fluconazole in an infection model induced by Candida albicans
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Universidade Federal de Minas Gerais
Descrição
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Artigo de periódico
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Membros da banca
Resumo
Background
Candida spp is an etiologic agent of fungal infections in hospitals and resistance to treatment with antifungals has been extensively reported. Thus, it is very important to develop formulations that increase effectiveness with low toxicity. In this sense, nanocarriers have been investigated, once they modify drug biodistribution profile. Thus, this study aimed to evaluate the biodistribution of free and encapsulated 99mTc-fluconazole into nanocapsules (NCs) in an experimental immunosuppressed murine model of Candida albicans infection.
Methods
Fluconazole was radiolabeled with technetium-99 metastable (99mTc) and encapsulated into conventional (99mTc-Fluconazole-PLA-POLOX) and surface-modified (99mTc-Fluconazole-PLA-PEG) NCs by the interfacial deposition of the preformed biodegradable polymer [poly (D,L-lactic acid) (PLA) and PLA–PEG (polyethyleneglycol)] followed by solvent evaporation. The size distribution and zeta potential of the NCs preparations were determined in a Zetasizer by photon correlation spectroscopy and laser Doppler anemometry, respectively. Free and encapsulated 99mTc-fluconazole were administered intravenously in immunosuppressed mice bearing a local infection induced by Candida Albicans inoculation in the right thigh muscle. At pre-established time intervals, tissues and organs of interest were removed and radioactivity was measured in an automatic gamma radiation counter.
Results
The NCs diameter was between 200 and 400 nm with negative zeta potential values. Free 99mTc-fluconazole was more rapidly eliminated by the renal system compared to the encapsulated drug in NCs, which remained longer in blood circulation. The uptake of conventional NCs by mononuclear phagocyte system organs was higher than the one demonstrated by the surface-modified NCs. Both NCs remained longer in the infectious focus when compared to free 99mTc-fluconazole, but the results did not show a significant difference between NC formulations.
Conclusion
These data indicate that these NCs might represent a therapeutic alternative for the treatment of candidiasis, once they remain more time in the infectious focus, allowing high retention of 99mTc-fluconazole at this site.
Abstract
Assunto
Candida albicans, Biodistribuição, Tecnécio-99 metaestável
Palavras-chave
Infectious focus, Biodistribution, Nanocapsules, Technetium-99 metastable, Fluconazole, Candida spp
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Endereço externo
https://www.sciencedirect.com/science/article/pii/S0753332217351478?via%3Dihub