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 synovitis and alleviates pain, albeit transiently. Biomaterial-based local TAA release may prolong the suppression 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 over 3 months. To evaluate their effect on pain and inflammation, TAA-loaded microspheres were intra-articularly delivered to the knee joint in a rat model of acute arthritis induced by intra-articular injection of streptococcal cell wall peptidoglycan-polysaccharide (PGPS) and subsequent flare-ups by intravenous PGPS injections. PEA-loaded microspheres were benchmarked with TAA-loaded PLGA microspheres and bolus TAA injection. TAA treatments were injected intra-articularly before the first induced flare-up. TAA-loaded PEA and PLGA microspheres reduced joint swelling and signs of pain-like behavior over the entire study period, as assessed by weight bearing and referred mechanical hypersensitivity, whereas bolus suspension was effective for a shorter time period. TAA-loaded PEA microspheres reduced lameness to a greater extent than TAA-loaded PLGA microspheres. In conclusion, a single intra-articular injection of TAA-loaded PEA microspheres reduced joint swelling and induced longer pain relief compared to bolus injection. Hence relief of inflammation and pain by PEA-based delivery of TAA may prove to be effective and durable.

中文翻译：

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关节内注射曲安奈德释放生物材料微球可抑制急性关节炎模型的疼痛和炎症。

滑膜和关节囊炎症是骨关节炎 (OA) 关节疼痛的主要原因。曲安奈德 (TAA) 是一种经典的皮质类固醇，可减少滑膜炎并减轻疼痛，尽管效果是短暂的。基于生物材料的局部 TAA 释放可以延长疼痛抑制时间，而无需多次注射。TAA 的聚乳酸-乙醇酸 (PLGA) 配方可在一定程度上延长 OA 疼痛的缓解时间。新型聚酯酰胺 (PEA) 微球平台可在 OA 关节中延长释放 3 个月以上。为了评估它们对疼痛和炎症的影响，将负载 TAA 的微球关节内递送至大鼠急性关节炎模型的膝关节，该模型是通过关节内注射链球菌细胞壁肽聚糖多糖 (PGPS) 诱导的，并随后引发急性关节炎通过静脉注射 PGPS。将负载 PEA 的微球与负载 TAA 的 PLGA 微球和推注 TAA 进行基准测试。在第一次诱发发作之前，关节内注射 TAA 治疗。通过负重和机械超敏反应评估，负载 TAA 的 PEA 和 PLGA 微球在整个研究期间减少了关节肿胀和疼痛样行为迹象，而推注悬浮液在较短的时间内有效。负载 TAA 的 PEA 微球比负载 TAA 的 PLGA 微球更大程度地减少跛行。总之，与推注相比，单次关节内注射负载 TAA 的 PEA 微球可减少关节肿胀并诱导更长时间的疼痛缓解。因此，通过基于 PEA 的 TAA 递送来缓解炎症和疼痛可能被证明是有效且持久的。