SAT0063 Effects of intra-articular injected diacerein-loaded nanoparticles on joint in rat model of osteoarthritis
Authors: J.H. Jung, G.G. Song, S.J. Choi, J.D. Ji, Y.H. Lee, J.-H. Kim
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Osteoarthritis (OA) is a major health problem in recent years, but the current medical treatment is mainly symptom control and joint disability improvement. Diacerein (DIA) reduces the level of interleukin (IL)−1 receptor on the surface of chondrocytes, alleviates the pain, and prevents the structural degradation of the joint tissue. However, DIA has the side effects such as diarrhoea and urine discoloration when taken orally. To increase bioavailability and reduce systemic side effects, it is preferable to inject DIA directly into the joints. Nanoparticulate drug carriers have been attempted with the advances in drug delivery systems. <h3>Objectives</h3> We investigated that DIA-loaded nanoparticles (DIA/NPs) can efficiently inhibit the inflammatory reaction in synoviocytes stimulated by lipopolysaccharide <i>in vitro</i> and alleviate both inflammation and cartilage degeneration in monosodium iodoacetate (MIA)-induced OA rat model <i>in vivo</i>. <h3>Methods</h3> DIA/NPs were fabricated by water/oil/water emulsion method. <i>In vitro,</i> the mRNA levels of pro-inflammatory cytokines (IL-1, IL-6, MMP-3, MMP-13, COX-2, ADAMTS-5, and TNF-α) were measured at 1 st and 3rd day after the administration of NPs only and DIA/NPs to synoviocytes using real-time PCR. MIA was intra-articular injected through the infrapatellar ligament of the rats' knee to induce OA. The rats were randomly divided into the six treatment groups:<sup>1</sup> control,<sup>2</sup> MIA,<sup>3</sup> MIA and NPs,<sup>4</sup> MIA and DIA(1%)/NPs,<sup>5</sup> MIA and DIA(5%)/NPs, and<sup>6</sup> MIA and DIA(5%) solution injection. After NPs, DIA(1%)/NPs, DIA(5%)/NPs, and DIA(5%) solution were injected, at 8th week, the rats were sacrificed to evaluate the plain radiographic and micro-computed tomography (micro-CT), histological study, and pro-inflammatory cytokines expression. <h3>Results</h3> The mRNA expression levels for pro-inflammatory cytokines in cells seeded with DIA(5%)/NPs and DIA(5%) solution were significantly lower than those in cells seeded with NPs at 1 st and 3rd day. Moreover, the mRNA levels of pro-inflammatory cytokines in cells injected with DIA(5%) solution decreased much greater than in cells injected with DIA(5%)/NPs. The rats injected DIA(5%)/NPs showed the least amount of cartilage and bone damage on plain radiography and micro-CT and had the less cartilage loss and the bony erosions on microscopic observation. The pro-inflammatory cytokines expression was lowest in the rats injected DIA(5%)/NPs, followed by NPs, DIA(1%)/NPs, and DIA(5%) solution. <h3>Conclusions</h3> DIA(5%)/NPs are a promising therapeutic material to control the symptoms and prevent the progression of OA. <h3>References</h3> [1] Jain A, et al. Diacerein protects against iodoacetate-induced osteoarthritis in the femorotibial joints of rats. J Biomed Res2015;29:405–413. [2] Bairwa K, et al. Nanoparticle formulation of 11-keto-β-boswellic acid (KBA): anti-inflammatory activity and in vivo pharmacokinetics. Pharm Biol2016;54:2909–2916. [3] Park JW, et al. Ibuprofen-loaded porous microspheres suppressed the progression of monosodium iodoacetate-induced osteoarthritis in a rat model. Colloids Surf B Biointerfaces2016;147:265–273. <h3>Acknowledgements</h3> No grants or other support were received for the conduction of this study. <h3>Disclosure of Interest</h3> None declared