Intra-articular injection of triamcinolone acetonide releasing biomaterial microspheres inhibits pain and inflammation in an acute arthritis model

摘要

Inflammation of the synovium and joint capsule is a main driver of pain in an osteoarthritic(OA) joint. Triamcinolone acetonide (TAA) is a classical corticosteroid that reduces synovitisand alleviates pain, albeit transiently. Biomaterial-based local TAA release may prolong thesuppression of pain without the need for multiple injections. Polylactic-co-glycolic acid(PLGA) formulations of TAA prolong OA pain relief to a limited extent. A novel polyesteramide(PEA) microsphere platform allows for extended release in the OA joint for over3 months. To evaluate their effect on pain and inflammation, TAA-loaded microspheres wereintra-articularly delivered to the knee joint in a rat model of acute arthritis induced by intraarticularinjection of streptococcal cell wall peptidoglycan-polysaccharide (PGPS) and subsequentflare-ups by intravenous PGPS injections. PEA-loaded microspheres were benchmarkedwith TAA-loaded PLGA microspheres and bolus TAA injection. TAA treatments were injectedintra-articularly before the first induced flare-up. TAA-loaded PEA and PLGA microspheresreduced joint swelling and signs of pain-like behavior over the entire study period, asassessed by weight bearing and referred mechanical hypersensitivity, whereas bolus suspensionwas effective for a shorter time period. TAA-loaded PEA microspheres reduced lamenessto a greater extent than TAA-loaded PLGA microspheres. In conclusion, a single intra-articularinjection of TAA-loaded PEA microspheres reduced joint swelling and induced longer painrelief compared to bolus injection. Hence relief of inflammation and pain by PEA-based deliveryof TAA may prove to be effective and durable.