Back to Journals » International Journal of Nanomedicine » Volume 9 » Issue 1

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

Authors 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

Received 7 June 2014

Accepted for publication 26 July 2014

Published 19 November 2014 Volume 2014:9(1) Pages 5341—5353

DOI https://doi.org/10.2147/IJN.S68966

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Thomas J Webster

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

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Other article by this author:

Novel targeting using nanoparticles: an approach to the development of an effective anti-leishmanial drug-delivery system

Ribeiro TG, Chávez-Fumagalli MA, Valadares DG, Franca JR, Rodrigues LB, Duarte MC, Lage PS, Andrade PHR, Lage DP, Arruda LV, Abánades DR, Costa LE, Martins VT, Tavares CAP, Castilho RO, Coelho EAF, Faraco AAG

International Journal of Nanomedicine 2014, 9:877-890

Published Date: 14 February 2014

Readers of this article also read:

A nanomedicine-promising approach to provide an appropriate colon-targeted drug delivery system for 5-fluorouracil

Singh S, Kotla NG, Tomar S, Maddiboyina B, Webster TJ, Sharma D, Sunnapu O

International Journal of Nanomedicine 2015, 10:7175-7182

Published Date: 23 November 2015

Molecular targets in arthritis and recent trends in nanotherapy

Roy K, Kanwar RK, Kanwar JR

International Journal of Nanomedicine 2015, 10:5407-5420

Published Date: 26 August 2015

Noninvasive detection of macrophages in atherosclerotic lesions by computed tomography enhanced with PEGylated gold nanoparticles

Qin J, Peng C, Zhao B, Ye K, Yuan F, Peng Z, Yang X, Huang L, Jiang M, Zhao Q, Tang G, Lu X

International Journal of Nanomedicine 2014, 9:5575-5590

Published Date: 2 December 2014

Gum arabic-coated radioactive gold nanoparticles cause no short-term local or systemic toxicity in the clinically relevant canine model of prostate cancer

Axiak-Bechtel SM, Upendran A, Lattimer JC, Kelsey J, Cutler CS, Selting KA, Bryan JN, Henry CJ, Boote E, Tate DJ, Bryan ME, Katti KV, Kannan R

International Journal of Nanomedicine 2014, 9:5001-5011

Published Date: 28 October 2014

Pluronic® L64-mediated stable HIF-1α expression in muscle for therapeutic angiogenesis in mouse hindlimb ischemia

Song H, Liu S, Li C, Geng Y, Wang G, Gu Z

International Journal of Nanomedicine 2014, 9:3439-3452

Published Date: 21 July 2014