Controlled release of celecoxib inhibits inflammation, bone cysts and osteophyte formation in a preclinical model of osteoarthritis

A. R. Tellegen, I. Rudnik-Jansen, B. Pouran, H. M. de Visser, H. H. Weinans, R. E. Thomas, M. J. L. Kik, G. C. M. Grinwis, J. C. Thies, N. Woike, G. Mihov, P. J. Emans, B. P. Meij, L. B. Creemers, M. A. Tryfonidou*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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 6days 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.
Original languageEnglish
Pages (from-to)1438-1447
Number of pages10
JournalDrug Delivery
Issue number1
Publication statusPublished - Nov 2018


  • Drug delivery
  • polyesteramide microspheres
  • synovitis
  • sclerosis
  • cartilage
  • COX-2
  • PAIN
  • RAT
  • RISK
  • Osteoarthritis/drug therapy
  • Bone and Bones/diagnostic imaging
  • Celecoxib/pharmacology
  • Cysts/drug therapy
  • Female
  • Cyclooxygenase 2 Inhibitors/pharmacology
  • Disease Models, Animal
  • Rats
  • Biocompatible Materials/pharmacology
  • Anterior Cruciate Ligament/drug effects
  • Delayed-Action Preparations/pharmacology
  • Animals
  • Osteophyte/drug therapy
  • Inflammation/drug therapy


Dive into the research topics of 'Controlled release of celecoxib inhibits inflammation, bone cysts and osteophyte formation in a preclinical model of osteoarthritis'. Together they form a unique fingerprint.

Cite this