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dc.contributor.authorBoechat, Antonio Luizpt_BR
dc.contributor.authorOliveira, Catiúscia Padilha dept_BR
dc.contributor.authorTarragô, Andrea Monteiropt_BR
dc.contributor.authorCosta, Allyson Guimarães dapt_BR
dc.contributor.authorMalheiro, Adrianapt_BR
dc.contributor.authorGuterres, Silvia Stanisçuaskipt_BR
dc.contributor.authorPohlmann, Adriana Raffinpt_BR
dc.date.accessioned2015-12-15T02:38:11Zpt_BR
dc.date.issued2015pt_BR
dc.identifier.issn1178-2013pt_BR
dc.identifier.urihttp://hdl.handle.net/10183/131131pt_BR
dc.description.abstractBackground: Rheumatoid arthritis (RA) is the most common autoimmune disease in the word, affecting 1% of the population. Long-term prognosis in RA was greatly improved following the introduction of highly effective medications such as methotrexate (MTX). Despite the importance of this drug in RA, 8%–16% of patients must discontinue the treatment because of adverse effects. Last decade, we developed a promising new nanocarrier as a drug-delivery system, lipid-core nanocapsules. Objective: The aim of the investigation reported here was to evaluate if methotrexate-loaded lipid-core nanocapsules (MTX-LNC) reduce proinflammatory and T-cell-derived cytokines in activated mononuclear cells derived from RA patients and even in functional MTX-resistant conditions. We also aimed to find out if MTX-LNC would reduce inflammation in experimentally inflammatory arthritis at lower doses than MTX solution. Methods: Formulations were prepared by self-assembling methodology. The adjuvant arthritis was induced in Lewis rats (AIA) and the effect on edema formation, TNF-α levels, and interleukin-1 beta levels after treatment was evaluated. Mononuclear cells obtained from the synovial fluid of RA patients during articular infiltration procedures were treated with MTX solution and MTX-LNC. For in vitro experiments, the same dose of MTX was used in comparing MTX and MTX-LNC, while the dose of MTX in the MTX-LNC was 75% lower than the drug in solution in in vivo experiments. Results: Formulations presented nanometric and unimodal size distribution profiles, with D[4.3] of 175±17 nm and span of 1.6±0.2. Experimental results showed that MTX-LNC had the same effect as MTX on arthritis inhibition on day 28 of the experiment (P,0.0001); however, this effect was achieved earlier, on day 21 (P,0.0001), by MTX-LNC, and this formulation had reduced both TNF-α (P=0.001) and IL-1a (P=0.0002) serum levels by the last day of the experiment. Further, the MTX-LNC were more effective at reducing the cytokine production from mononuclear synovial cells than MTX. Conclusion: The MTX-LNC were better than the MTX solution at reducing proinflammatory cytokines and T-cell-derived cytokines such as interferon-gamma and interleukin-17A. This result, combined with the reduction in the dose required for therapy, shows that MTX-LNC are a very promising system for the treatment of RA.en
dc.format.mimetypeapplication/pdf
dc.language.isoengpt_BR
dc.relation.ispartofInternational Journal of Nanomedicine. Manchester. Vol. 10, no. 1 (Oct. 2015), p. 6603-6614pt_BR
dc.rightsOpen Accessen
dc.subjectDrug deliveryen
dc.subjectArtritept_BR
dc.subjectDrug targetingen
dc.subjectCitocinaspt_BR
dc.subjectArthritisen
dc.subjectMetotrexatopt_BR
dc.subjectCytokinesen
dc.subjectTNF-αen
dc.subjectIL-6en
dc.subjectIL-1en
dc.subjectIL-17Aen
dc.subjectIFN-γen
dc.titleMethotrexate-loaded lipid-core nanocapsules are highly effective in the control of inflammation in synovial cells and a chronic arthritis modelpt_BR
dc.typeArtigo de periódicopt_BR
dc.identifier.nrb000980822pt_BR
dc.type.originEstrangeiropt_BR


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