Controlled release of celecoxib inhibits inflammation, bone cysts and osteophyte formation in a preclinical model of osteoarthritis
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 del...
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doaj-b16740c3a54b4b8abb5bd8bf3ebd323a2020-11-25T03:27:17ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642018-01-012511438144710.1080/10717544.2018.14829711482971Controlled release of celecoxib inhibits inflammation, bone cysts and osteophyte formation in a preclinical model of osteoarthritisA. R. Tellegen0I. Rudnik-Jansen1B. Pouran2H. M. de Visser3H. H. Weinans4R. E. Thomas5M. J. L. Kik6G. C. M. Grinwis7J. C. Thies8N. Woike9G. Mihov10P. J. Emans11B. P. Meij12L. B. Creemers13M. A. Tryfonidou14Utrecht UniversityUniversity Medical Centre UtrechtUniversity Medical Centre UtrechtUniversity Medical Centre UtrechtUniversity Medical Centre UtrechtUtrecht UniversityUtrecht UniversityUtrecht UniversityDSM BiomedicalDSM BiomedicalDSM BiomedicalUniversity Medical Centre MaastrichtUtrecht UniversityUniversity Medical Centre UtrechtUtrecht UniversityMajor 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 6 days 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.http://dx.doi.org/10.1080/10717544.2018.1482971drug deliverypolyesteramide microspheressynovitissclerosiscartilagecox-2 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Controlled release of celecoxib inhibits inflammation, bone cysts and osteophyte formation in a preclinical model of osteoarthritis Drug Delivery drug delivery polyesteramide microspheres synovitis sclerosis cartilage cox-2 |
author_facet |
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 |
author_sort |
A. R. Tellegen |
title |
Controlled release of celecoxib inhibits inflammation, bone cysts and osteophyte formation in a preclinical model of osteoarthritis |
title_short |
Controlled release of celecoxib inhibits inflammation, bone cysts and osteophyte formation in a preclinical model of osteoarthritis |
title_full |
Controlled release of celecoxib inhibits inflammation, bone cysts and osteophyte formation in a preclinical model of osteoarthritis |
title_fullStr |
Controlled release of celecoxib inhibits inflammation, bone cysts and osteophyte formation in a preclinical model of osteoarthritis |
title_full_unstemmed |
Controlled release of celecoxib inhibits inflammation, bone cysts and osteophyte formation in a preclinical model of osteoarthritis |
title_sort |
controlled release of celecoxib inhibits inflammation, bone cysts and osteophyte formation in a preclinical model of osteoarthritis |
publisher |
Taylor & Francis Group |
series |
Drug Delivery |
issn |
1071-7544 1521-0464 |
publishDate |
2018-01-01 |
description |
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 6 days 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. |
topic |
drug delivery polyesteramide microspheres synovitis sclerosis cartilage cox-2 |
url |
http://dx.doi.org/10.1080/10717544.2018.1482971 |
work_keys_str_mv |
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1724588505481347072 |