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
| Autor: | Eduardo A.F. Coelho, Lourena E. Costa, Manuel Soto, Vívian T. Martins, Leonardo Lima Fuscaldi, Mariana C. Duarte, Paula S. Lage, Rachel Oliveira Castilho, Carlos Alberto Pereira Tavares, Valbert Nascimento Cardoso, Simone Odília Antunes Fernandes, Miguel A. Chávez-Fumagalli, Tatiana G. Ribeiro, André Augusto Gomes Faraco, Juçara R. Franca, Mara Lívia dos Santos |
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| Přispěvatelé: | UAM. Departamento de Biología Molecular |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Biodistribution
Chondroitin sulfate Materials science Biophysics Antiprotozoal Agents Pharmaceutical Science Bioengineering Spleen Pharmacology Kidney Biomaterials chemistry.chemical_compound Mice International Journal of Nanomedicine Amphotericin B Drug Discovery medicine in vivo treatment Animals Tissue Distribution Leishmaniasis Original Research chondroitin sulfate Leishmania Chitosan Mice Inbred BALB C biology Organic Chemistry Chondroitin Sulfates General Medicine biology.organism_classification medicine.disease Biología y Biomedicina / Biología In vivo treatment medicine.anatomical_structure chemistry Immunology Toxicity Nanoparticles Female medicine.drug Leishmania amazonensis |
| Zdroj: | International Journal of Nanomedicine Digital.CSIC. Repositorio Institucional del CSIC instname Biblos-e Archivo. Repositorio Institucional de la UAM |
| ISSN: | 1178-2013 1176-9114 |
| Popis: | 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. 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). |
| Databáze: | OpenAIRE |
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