Dados do Trabalho

Title

DICLOFENAC LIPID-CORE NANOCAPSULES ARE EFFECTIVE TO CONTROL EXPERIMENTAL ARTHRITIS AND MONONUCLEAR CELLS INFLAMMATION

Background

Diclofenac is a widely used non-steroidal anti-inflammatory drug to inflammation and pain control for rheumatoid arthritis and spondyloarthritis. However, the use of diclofenac is related to serious adverse effects. We developed this new diclofenac formulation - a diclofenac lipid-core nanocapsule as a promising effective and safe formulation. The aim of this work was to evaluate if diclofenac -loaded lipid-core nanocapsules reduce experimental arthritis and proinflammatory and T-cell-derived cytokines in activated mononuclear cells derived from RA patients.

Materials and methods

Formulations were prepared by self-assembling methodology. Adjuvant arthritis was induced in Lewis rats (AIA) and the effect on edema formation, TNF-alfa levels, interleukin-1 beta (IL1), C-Reactive protein levels (CRP) after treatment were evaluated. Mononuclear cells obtained from the synovial fluid of RA patients during infiltration procedures were treated with Diclofenac (DIC) solution and diclofenac lipid-core nanocapsules (DIC-LNC). TNF-alfa and IL6 cytokine levels were quantified at supernatant cultures from RA patients derived mononuclear cells. DIC-LNC reduced IL17 cytokine (r = 0.98, p=0.001) production on mononuclear cells culture in a dose-dependent manner compared to DIC.

Results

Formulations showed nanometric and unimodal size distribution profiles with D[4.3] of 204±46 and span of 1.7±0.1. At the 28th day of the experiment the DIC-LNC, the hind paw volume was reduced than DIC (p <0.05) and arthritis group (p<0.05). We also observed an early edema inhibition on the 21st day of the experiment by DIN-LNC and we DIC formulation did not show similar properties. Inflammatory biomarkers TNF-alfa, IL1 and CRP (p <0.05 ) were significantly reduced for DIC-LNC (p<0.05) compared to DIC group (p <0.05). Interesting, TNF-alfa, IL-6 and IL17 cytokines produced by synovial mononuclear cells were also reduced compared to arthritis group (p <0.05) and conventional DIC (p <0.05).

Conclusions

Diclofenac lipid-core nanocapsules were more effective than common diclofenac formulation for inflammation control, reducing paw edema formation and TNF-alfa and IL1 cytokine levels, as well as the synovial cells TNF-alfa, IL-6, and IL17 cytokine production. These are promising features in the field of rheumatology especially for inflammatory arthritis, improving the quality and efficiency of a Diclofenac.