Abstract
Major hallmarks of osteoarthritis (OA) are cartilage degeneration, inflammation and osteophyte formation. COX-2 inhibitors counteract inflammation-related pain, but their prolonged oral use entails the risk for side effects. Local and prolonged administration in biocompatible and degradable drug delivery biomaterials could offer an efficient and safe treatment for the long-term management of OA symptoms. Therefore, we evaluated the disease-modifying effects and the optimal dose of polyesteramide microspheres delivering the COX-2 inhibitor celecoxib in a rat OA model. Four weeks after OA induction by anterior cruciate ligament transection and partial medial meniscectomy, 8-week-old female rats (n = 6/group) were injected intra-articular with celecoxib-loaded microspheres at three dosages (0.03, 0.23 or 0.39 mg). Unloaded microspheres served as control. During the 16-week follow-up, static weight bearing and plasma celecoxib concentrations were monitored. Post-mortem, micro-computed tomography and knee joint histology determined progression of synovitis, osteophyte formation, subchondral bone changes, and cartilage integrity. Systemic celecoxib levels were below the detection limit 6 days upon delivery. Systemic and local adverse effects were absent. Local delivery of celecoxib reduced the formation of osteophytes, subchondral sclerosis, bone cysts and calcified loose bodies, and reduced synovial inflammation, while cartilage histology was unaffected. Even though the effects on pain could not be evualated directly in the current model, our results suggest the application of celecoxib-loaded microspheres holds promise as novel, safe and effective treatment for inflammation and pain in OA.
Highlights
Osteoarthritis (OA) is the most common form of arthritis in humans
Even though the effects on pain could not be evualated directly in the current model, our results suggest the application of celecoxib-loaded microspheres holds promise as novel, safe and effective treatment for inflammation and pain in OA
Subchondral bone changes are considered increasingly important in OA
Summary
Osteoarthritis (OA) is the most common form of arthritis in humans. It is estimated that 18% of women and 10% of men over the age of 60 years suffer from OA (Cross et al, 2014). Bone marrow lesions (BML) and subchondral bone cysts appear early in the disease process (Alliston et al, 2017) and are visible as regions of hyperintense marrow signal in fluid-sensitive MRI image sequences (Kon et al, 2016). Both have been associated with joint pain (Yusuf et al, 2011) and disease progression (Taljanovic et al, 2008; Tanamas et al, 2010). OA is considered a disease of the whole joint and successful therapeutic strategies
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