Dextran sulfate-triamcinolone acetonide conjugate nanoparticles for targeted treatment of osteoarthritis.

Osteoarthritis (OA) is a synovial inflammatory condition characterized by cartilage destruction and osteophyte formation. Macrophages play a central role in OA pathogenesis by producing proinflammatory cytokines. Intra-articular corticosteroid administration can relieve refractory pain and inflamed effusion of knee joints. However, limitations, such as rapid clearance from the joint space, potential damage to articular cartilage, and ac-celerated joint degeneration, may hamper the clinical application of corticosteroids. In this study, we reported the design and preparation of dextran sulfate-triamcinolone acetonide conjugate (DS-TA) nanoparticles (NPs) for treating OA by specifically targeting scavenger receptor class A (SR-A) on activated macrophages. We verified the excellent targeting specificity of DS-TA NPs to SR-A by flow cytometry and confocal laser scanning micros-copy. DS-TA NPs were found to effectively reduce the viability of activated macrophages (RAW 264.7 cells) and the expression of proinflammatory cytokines. Intra-articular injection of DS-TA NPs effectively alleviated the structural damages to the joint cartilage, as confirmed in histopathological analysis. Additionally, DS-TA NPs decreased the expression of proinflammatory cytokines, including IL-1 beta, IL-6, and TNF-alpha, in the cartilage tissue. Thus, DS-TA NPs are a potential therapeutic nanomedicine for the targeted treatment of OA. (C) 2020 Published by Elsevier B.V.