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

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

Tatiana G Ribeiro,1 Juçara R Franca,1 Leonardo L Fuscaldi,1 Mara L Santos,2 Mariana C Duarte,3 Paula S Lage,3 Vivian T Martins,4 Lourena E Costa,3 Simone OA Fernandes,1,5 Valbert N Cardoso,1,5 Rachel O Castilho,1,6 Manuel Soto,7 Carlos AP Tavares,4 André AG Faraco,1,6 Eduardo...

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Autores principales: Ribeiro TG, Franca JR, Fuscaldi LL, Santos ML, Duarte MC, Lage PS, Martins VT, Costa LE, Fernandes SOA, Cardoso VN, Castilho RO, Soto M, Tavares CAP, Faraco AAG, Coelho EAF, Chávez-Fumagalli MA
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2014
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Medicine (General)
R5-920
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spelling oai:doaj.org-article:d90b05ef41714339afe2dfc340abc7472021-12-02T02:31:35ZAn optimized nanoparticle delivery system based on chitosan and chondroitin sulfate molecules reduces the toxicity of amphotericin B and is effective in treating tegumentary leishmaniasis1178-2013https://doaj.org/article/d90b05ef41714339afe2dfc340abc7472014-11-01T00:00:00Zhttp://www.dovepress.com/an-optimized-nanoparticle-delivery-system-based-on-chitosan-and-chondr-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Tatiana G Ribeiro,1 Juçara R Franca,1 Leonardo L Fuscaldi,1 Mara L Santos,2 Mariana C Duarte,3 Paula S Lage,3 Vivian T Martins,4 Lourena E Costa,3 Simone OA Fernandes,1,5 Valbert N Cardoso,1,5 Rachel O Castilho,1,6 Manuel Soto,7 Carlos AP Tavares,4 André AG Faraco,1,6 Eduardo AF Coelho,3,8,* Miguel A Chávez-Fumagalli3,* 1Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, 2Departamento de Morfologia, Instituto de Ciências Biológicas, 3Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, 4Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, 5Departamento de Análises Clínicas e Toxicológicas, 6Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; 7Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Departamento de Biología Molecular, Universidad Autónoma de Madrid, Madrid, Spain; 8Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil *These authors contributed equally to this work Abstract: 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. Keywords: in vivo treatment, Leishmania amazonensis, nanoparticles, chitosan, chondroitin sulfateRibeiro TGFranca JRFuscaldi LLSantos MLDuarte MCLage PSMartins VTCosta LEFernandes SOACardoso VNCastilho ROSoto MTavares CAPFaraco AAGCoelho EAFChávez-Fumagalli MADove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 5341-5353 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Ribeiro TG
Franca JR
Fuscaldi LL
Santos ML
Duarte MC
Lage PS
Martins VT
Costa LE
Fernandes SOA
Cardoso VN
Castilho RO
Soto M
Tavares CAP
Faraco AAG
Coelho EAF
Chávez-Fumagalli MA
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
description Tatiana G Ribeiro,1 Juçara R Franca,1 Leonardo L Fuscaldi,1 Mara L Santos,2 Mariana C Duarte,3 Paula S Lage,3 Vivian T Martins,4 Lourena E Costa,3 Simone OA Fernandes,1,5 Valbert N Cardoso,1,5 Rachel O Castilho,1,6 Manuel Soto,7 Carlos AP Tavares,4 André AG Faraco,1,6 Eduardo AF Coelho,3,8,* Miguel A Chávez-Fumagalli3,* 1Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, 2Departamento de Morfologia, Instituto de Ciências Biológicas, 3Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, 4Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, 5Departamento de Análises Clínicas e Toxicológicas, 6Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; 7Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Departamento de Biología Molecular, Universidad Autónoma de Madrid, Madrid, Spain; 8Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil *These authors contributed equally to this work Abstract: 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. Keywords: in vivo treatment, Leishmania amazonensis, nanoparticles, chitosan, chondroitin sulfate
format article
author Ribeiro TG
Franca JR
Fuscaldi LL
Santos ML
Duarte MC
Lage PS
Martins VT
Costa LE
Fernandes SOA
Cardoso VN
Castilho RO
Soto M
Tavares CAP
Faraco AAG
Coelho EAF
Chávez-Fumagalli MA
author_facet Ribeiro TG
Franca JR
Fuscaldi LL
Santos ML
Duarte MC
Lage PS
Martins VT
Costa LE
Fernandes SOA
Cardoso VN
Castilho RO
Soto M
Tavares CAP
Faraco AAG
Coelho EAF
Chávez-Fumagalli MA
author_sort Ribeiro TG
title 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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort optimized nanoparticle delivery system based on chitosan and chondroitin sulfate molecules reduces the toxicity of amphotericin b and is effective in treating tegumentary leishmaniasis
publisher Dove Medical Press
publishDate 2014
url https://doaj.org/article/d90b05ef41714339afe2dfc340abc747
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