Localized Delivery of Nanoemulsified Curcumin Ameliorates Joint Edema, Cartilage Fibrillation and Synovial Inflammation in the Osteoarthritis Model, and Macrophage Recruitment in Stimulated Chondrocytes

The pathogenesis of knee osteoarthritis (OA) is multifaceted and involves the complete joint microenvironment. Despite beneficial evidence of curcumin, the mechanistic insights of nanoemulsified curcumin (n-Cur) delivery to the knee-OA microenvironment are limited. A detailed histological change that occurs in the knee joint of the OA model after localized delivery of curcumin was examined. n-Cur was prepared using a neutral dietary oil and a surfactant. Adult (5 mo) male SD rats were intra-articularly delivered 40 mg/ml of monoiodoacetate (MIA) to induce OA in the left knee and further treated with n-Cur (30 mg/ml). The effect of n-Cur on macrophage recruitment was evaluated using a co-culture model of CHON 001 and RAW 264.7 cells. In the MIA-model, localized delivery of n-Cur significantly reduced knee-joint edema, and articular cavity stenosis in the target site. Curcumin ameliorated cartilage degeneration by reducing fibrillation, hypocellularity, and restoring matrix proteoglycan, as evidenced by histology. Reduced synovial inflammation displays the effect of curcumin on the synovium, possibly by lowering the recruitment of macrophages in chemoattractant-stimulated chondrocytes. Thus, curcumin nanoemulsion can act as a chondroprotective agent, modulating the OA microenvironment by reducing joint edema, synovial inflammation, and oxidative stress in the OA model.