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Sustained release of locally delivered celecoxib provides pain relief for osteoarthritis: a proof of concept in dog patients.
Tellegen, A R; Rudnik-Jansen, I; Utomo, L; Versteeg, S; Beukers, M; Maarschalkerweerd, R; van Zuilen, D; van Klaveren, N J; Houben, K; Teske, E; van Weeren, P R; Karssemakers-Degen, N; Mihov, G; Thies, J; Eijkelkamp, N; Creemers, L B; Meij, B P; Tryfonidou, M A.
Afiliación
  • Tellegen AR; Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
  • Rudnik-Jansen I; Department of Orthopedics, University Medical Centre Utrecht, Utrecht, the Netherlands.
  • Utomo L; Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
  • Versteeg S; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.
  • Beukers M; Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
  • Maarschalkerweerd R; Department of Orthopedics, Medisch Centrum voor Dieren, Amsterdam, the Netherlands.
  • van Zuilen D; Department of Orthopedics, Medisch Centrum voor Dieren, Amsterdam, the Netherlands.
  • van Klaveren NJ; Department of Orthopedics, Medisch Centrum voor Dieren, Amsterdam, the Netherlands.
  • Houben K; Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
  • Teske E; Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
  • van Weeren PR; Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
  • Karssemakers-Degen N; DSM Biomedical, Geleen, the Netherlands.
  • Mihov G; DSM Biomedical, Geleen, the Netherlands.
  • Thies J; DSM Biomedical, Geleen, the Netherlands.
  • Eijkelkamp N; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.
  • Creemers LB; Department of Orthopedics, University Medical Centre Utrecht, Utrecht, the Netherlands.
  • Meij BP; Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
  • Tryfonidou MA; Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands. Electronic address: m.a.tryfonidou@uu.nl.
Osteoarthritis Cartilage ; 31(3): 351-362, 2023 03.
Article en En | MEDLINE | ID: mdl-36473675
OBJECTIVE: Drug delivery platforms that allow for gradual drug release after intra-articular administration have become of much interest as a treatment strategy for osteoarthritis (OA). The aim of this study was to investigate the safety and efficacy of an intra-articular sustained release formulation containing celecoxib (CXB), a cyclooxygenase-2 (COX-2) selective inhibitor. METHODS: Amino acid-based polyesteramide microspheres (PEAMs), a biodegradable and non-toxic platform, were loaded with CXB and employed in two in vivo models of arthritis: an acute inflammatory arthritis model in rats (n = 12), and a randomized controlled study in chronic OA dog patients (n = 30). In parallel, the bioactivity of sustained release of CXB was evaluated in monolayer cultures of primary dog chondrocytes under inflammatory conditions. RESULTS: Sustained release of CXB did not alleviate acute arthritis signs in the rat arthritis model, based on pain measurements and synovitis severity. However, in OA dog patients, sustained release of CXB improved limb function as objective parameter of pain and quality of life based on gait analysis and owner questionnaires. It also decreased pain medication dependency over a 2-month period and caused no adverse effects. Prostaglandin E2 levels, a marker for inflammation, were lower in the synovial fluid of CXB-treated dog OA patients and in CXB-treated cultured dog chondrocytes. CONCLUSION: These results show that local sustained release of CXB is less suitable to treat acute inflammation in arthritic joints, while safe and effective in treating pain in chronic OA in dogs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoartritis / Calidad de Vida Tipo de estudio: Clinical_trials Aspecto: Patient_preference Límite: Animals Idioma: En Revista: Osteoarthritis Cartilage Asunto de la revista: ORTOPEDIA / REUMATOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoartritis / Calidad de Vida Tipo de estudio: Clinical_trials Aspecto: Patient_preference Límite: Animals Idioma: En Revista: Osteoarthritis Cartilage Asunto de la revista: ORTOPEDIA / REUMATOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido