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Antônio Luiz Boechat,1,2,* Catiúscia Padilha de Oliveira,3,* Andrea Monteiro Tarragô,2 Allyson Guimarães da Costa,2 Adriana Malheiro,1,2 Silvia Stanisçuaski Guterres,3 Adriana Raffin Pohlmann3,41Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal do Amazonas, Manaus, 2Programa de Pós-Graduação e Imunologia Básica e Aplicada, Universidade Federal do Amazonas, Manaus, 3Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, 4Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil*These authors contributed equally to this workBackground: 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-a 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 |
