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

Drug Delivery

Nina Woike¹  Jens Thies¹  George Mihov¹  Anna Tellegen²  Marianna Tryfonidou²  Pieter Emans³  Imke Rudnik-Jansen⁴  Karin Schrijver⁴  Laura Creemers⁴  Niels Eijkelkamp⁵  Sabine Versteeg⁵ 

[1] DSM Biomedical B.V, Geleen, The Netherlands;Department of Clinical Sciences of Companion Animals, Utrecht University, Utrecht, the Netherlands;Department of Orthopedics, Maastricht University Medical Center Utrecht, Utrecht, the Netherland;Department of Orthopedics, University Medical Center Utrecht, Utrecht, the Netherlands;Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands;

关键词: Arthritis;    microspheres;    polyesteramide;    polylactic-co-glycolic acid;    synovitis;    triamcinolone acetonide;   

DOI  :  10.1080/10717544.2019.1568625

来源: publisher

【 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 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.

【 授权许可】

CC BY