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Sustained release of locally delivered celecoxib provides pain relief for osteoarthritis: a proof of concept in dog patients.

Authors :
Tellegen AR
Rudnik-Jansen I
Utomo L
Versteeg S
Beukers M
Maarschalkerweerd R
van Zuilen D
van Klaveren NJ
Houben K
Teske E
van Weeren PR
Karssemakers-Degen N
Mihov G
Thies J
Eijkelkamp N
Creemers LB
Meij BP
Tryfonidou MA
Source :
Osteoarthritis and cartilage [Osteoarthritis Cartilage] 2023 Mar; Vol. 31 (3), pp. 351-362. Date of Electronic Publication: 2022 Dec 05.
Publication Year :
2023

Abstract

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.<br />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.<br />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 E <subscript>2</subscript> levels, a marker for inflammation, were lower in the synovial fluid of CXB-treated dog OA patients and in CXB-treated cultured dog chondrocytes.<br />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.<br /> (Copyright © 2022 Utrecht University. Published by Elsevier Ltd.. All rights reserved.)

Details

Language :
English
ISSN :
1522-9653
Volume :
31
Issue :
3
Database :
MEDLINE
Journal :
Osteoarthritis and cartilage
Publication Type :
Academic Journal
Accession number :
36473675
Full Text :
https://doi.org/10.1016/j.joca.2022.11.008