A comparative pilot study of oral diacerein and locally treated diacerein-loaded nanoparticles in a model of osteoarthritis.

Diacerein (DIA) is a slow-acting drug for osteoarthritis (OA). Oral DIA administration, however, exerts side effects including diarrhea and urine discoloration. We fabricated DIA-loaded poly(d,l-lactide-co-glycolide) nanoparticles (DIA/PLGA NPs) that allow sustained release of DIA. In vitro, rat synoviocytes were used to investigate the cytotoxicity and anti-inflammatory effects of DIA-loaded NPs. In vivo, monosodium iodoacetate (MIA)-induced OA rats were divided into seven groups that included non-treated healthy control rats and rats injected with MIA alone or in combination with NPs, DIA(5%) solution, DIA(1%)/NPs, DIA(5%)/NPs, or oral DIA. The in vitro studies revealed that DIA/PLGA NPs dose-dependently suppressed mRNA levels of pro-inflammatory cytokines and enzymes, including interleukin-1 (IL-1), IL-6, tumor necrosis factor-α, matrix metalloproteinase-3 (MMP-3), MMP-13, cyclo-oxygenase-2, and a disintegrin and metalloproteinase with thrombospondin motifs-5 in synoviocytes. The in vivo studies demonstrated that intra-articular treatment of OA rat models with DIA-loaded PLGA NPs markedly decreased mRNA levels of these pro-inflammatory factors and increased those of anti-inflammatory cytokines (IL-4 and IL-10). Micro-computed tomography and histological evaluations indicated that intra-articular injection of DIA-loaded NPs was effective in protecting against cartilage degradation. Administration of DIA/PLGA NPs via intra-articular injection is promising for inhibiting inflammation and protecting against cartilage degradation in OA.