An optimized nanoparticle delivery system based on chitosan and chondroitin sulfate molecules reduces the toxicity of amphotericin B and is effective in treating tegumentary leishmaniasis
Author
Ribeiro, Tatiana G.; Franca, Juçara R.; Fuscaldi, Leonardo L.; Santos, Mara L.; Duarte, Mariana C.; Lage, Paula S.; Martins, Vivian T.; Costa, Lourena E.; Fernandes, Simone O.A.; Cardoso, Valbert N.; Castilho, Rachel O.; Soto Álvarez, Manuel; Tavares, Carlos A.P.; Faraco, André A.G.; Coelho, Eduardo A.F.; Chávez-Fumagalli, Miguel A.Entity
UAM. Departamento de Biología MolecularPublisher
Dove Medical Press Ltd.(DovePress)Date
2014-01-01Citation
10.2147/IJN.S68966
International Journal of Nanomedicine 2014.9 (2014): 5341-5353
ISSN
1176-9114 (print); 1178-2013 (online)DOI
10.2147/IJN.S68966Funded by
This work was supported by grants from Pró-Reitoria de Pesquisa from UFMG (Edital 01/2014), Instituto Nacional de Ciência e Tecnologia em Nano-biofarmacêutica (INCT-Nanobiofar), FAPEMIG (CBB-APQ-00496-11 and CBB-APQ-00819-12), and CNPq (APQ-472090/2011-9 and APQ-482976/2012-8). MACF is a grant recipient of FAPEMIG/CAPES. EAFC, VNC, and AAGF are grant recipients of CNPq. Eduardo AF Coelho and André AG Faraco are co-senior authors of this studyEditor's Version
https://doi.org/10.2147/IJN.S68966Subjects
Chitosan; Chondroitin sulfate; In vivo treatment; Leishmania amazonensis; Nanoparticles; Biología y Biomedicina / BiologíaRights
© 2014 Ribeiro et alAbstract
Amphotericin B (AmpB) is active against leishmaniasis, but its use is hampered due to its high toxicity observed in patients. In this study, a nanoparticles-delivery system for AmpB (NQC-AmpB), containing chitosan and chondroitin sulfate molecules, was evaluated in BALB/c mice against Leishmania amazonensis. An in vivo biodistribution study, including biochemical and toxicological evaluations, was performed to evaluate the toxicity of AmpB. Nanoparticles were radiolabeled with technetium-99m and injected in mice. The products presented a similar biodistribution in the liver, spleen, and kidneys of the animals. Free AmpB induced alterations in the body weight of the mice, which, in the biochemical analysis, indicated hepatic and renal injury, as well as morphological damage to the kidneys of the animals. In general, no significant organic alteration was observed in the animals treated with NQC-AmpB. Mice were infected with L. amazonensis and treated with the nanoparticles or free AmpB; then, parasitological and immunological analyses were performed. The NQC-AmpB group, as compared to the control groups, presented significant reductions in the lesion size and in the parasite burden in all evaluated organs. These animals presented significantly higher levels of IFN-γ and IL-12, and low levels of IL-4 and IL-10, when compared to the control groups. The NQC-AmpB system was effective in reducing the infection in the animals, and proved to be effective in diminishing the toxicity evoked by AmpB, which was observed when it was administered alone. In conclusion, NQC-AmpB could be considered a viable possibility for future studies in the treatment of leishmaniasis
Files in this item
Google Scholar:Ribeiro, Tatiana G.
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Franca, Juçara R.
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Fuscaldi, Leonardo L.
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Santos, Mara L.
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Duarte, Mariana C.
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Lage, Paula S.
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Martins, Vivian T.
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Costa, Lourena E.
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Fernandes, Simone O.A.
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Cardoso, Valbert N.
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Castilho, Rachel O.
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Soto Álvarez, Manuel
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Tavares, Carlos A.P.
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Faraco, André A.G.
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Coelho, Eduardo A.F.
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Chávez-Fumagalli, Miguel A.
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