TY - JOUR
T1 - Sustained release of locally delivered celecoxib provides pain relief for osteoarthritis
T2 - a proof of concept in dog patients
AU - Tellegen, Anna R
AU - Rudnik-Jansen, Imke
AU - Utomo, Lizette
AU - Versteeg, Sabine
AU - Beukers, Martijn
AU - Maarschalkerweerd, Roelof
AU - van Zuilen, Dick
AU - van Klaveren, Nicoline J
AU - Houben, Kaat
AU - Teske, Erik
AU - René van Weeren, P
AU - Karssemakers-Degen, Nina
AU - Mihov, George
AU - Thies, Jens
AU - Eijkelkamp, Niels
AU - Creemers, Laura B
AU - Meij, Björn P
AU - Tryfonidou, Marianna A
N1 - Funding Information:
This work was financially supported by a research grant from Life Sciences Health (LSH) Impulse, (ArIADNE; project #40-43100-98-022). The financial contribution of the Dutch Arthritis Society is also gratefully acknowledged (LLP22 and LLP12).
Funding Information:
This work was financially supported by a research grant from Life Sciences Health (LSH) Impulse , (ArIADNE; project #40-43100-98-022). The financial contribution of the Dutch Arthritis Society is also gratefully acknowledged (LLP22 and LLP12).
Publisher Copyright:
© 2022 Utrecht University
PY - 2023/3
Y1 - 2023/3
N2 - 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 E
2 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.
AB - 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 E
2 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.
KW - Controlled release
KW - Inflammation
KW - Non-steroidal anti-inflammatory drugs
KW - Osteoarthritis
KW - Pain
UR - http://www.scopus.com/inward/record.url?scp=85144972370&partnerID=8YFLogxK
U2 - 10.1016/j.joca.2022.11.008
DO - 10.1016/j.joca.2022.11.008
M3 - Article
C2 - 36473675
SN - 1063-4584
VL - 31
SP - 351
EP - 362
JO - Osteoarthritis and Cartilage
JF - Osteoarthritis and Cartilage
IS - 3
ER -