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

Imke Rudnik-Jansen, Karin Schrijver, Nina Woike, Anna Tellegen, Sabine Versteeg, Pieter Emans, George Mihov, Jens Thies, Niels Eijkelkamp, Marianna Tryfonidou, Laura Creemers*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

27 Citations (Web of Science)

Abstract

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.

Original languageEnglish
Pages (from-to)226-236
Number of pages11
JournalDrug Delivery
Volume26
Issue number1
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • Arthritis
  • CARTILAGE
  • CELECOXIB
  • DRUG-DELIVERY
  • EFFICACY
  • GLUCOCORTICOIDS
  • KNEE
  • OSTEOARTHRITIS PATIENTS
  • RAT MODEL
  • SYNOVITIS
  • SYSTEM
  • microspheres
  • polyesteramide
  • polylactic-co-glycolic acid
  • synovitis
  • triamcinolone acetonide
  • FORMULATION

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