Shape-Defined Microplates For The Sustained Intra-Articular Release Of Dexamethasone In The Management Of Overload-Induced Osteoarthritis

Osteoarthritis (OA) is treated with the intra-articular injection of steroids such as dexamethasone (DEX) to provide short-term pain management. However, DEX treatment suffers from rapid joint clearance. Here, 20 x 10 mu m, shape-defined poly(D,L-lactide-co-glycolide)acid microPlates (mu PLs) are created and intra-articularly deposited for the sustained release of DEX. Under confined conditions, DEX release is projected to persist for several months, with only similar to 20% released in the first month. In a highly rigorous murine knee overload injury model (post-traumatic osteoarthritis), a single intra-articular injection of Cy5-mu PLs is detected in the cartilage surface, infrapatellar fat pad/synovium, joint capsule, and posterior joint space up to 30 days. One intra-articular injection of DEX-mu PL (1 mg kg(-1)) decreased the expression of interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, IL-6, and matrix metalloproteinase (MMP)-13 by approximately half compared to free DEX at 4 weeks post-treatment. DEX-mu PL also reduced load-induced histological changes in the articular cartilage and synovial tissues relative to saline or free DEX. In sum, the mu PLs provide sustained drug release along with the capability to precisely control particle geometry and mechanical properties, yielding long-lasting benefits in overload-induced OA. This work motivates further study and development of particles that provide combined pharmacological and mechanical benefits.