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European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V2018; 128; 327-336; doi: 10.1016/j.ejpb.2018.05.001

Sustained intra-articular release of celecoxib in an equine repeated LPS synovitis model.

Abstract: Synovial inflammation is an important characteristic of arthritic disorders like osteoarthritis and rheumatoid arthritis. Orally administered non-steroidal anti-inflammatory drugs (NSAIDs) such as celecoxib are among the most widely prescribed drugs to manage these debilitating diseases. Intra-articular delivery in biodegradable in situ forming hydrogels overcomes adverse systemic effects and prolongs drug retention in the joint. In this study two formulations of celecoxib (40 mg/g and 120 mg/g) in a propyl-capped PCLA-PEG-PCLA triblock copolymer were sequentially evaluated in a multiple LPS challenge equine synovitis model. Intra-articular release and systemic exposure to celecoxib and local changes at joint level were evaluated longitudinally. A single intra-articular injection of the high dose (HCLB)-gel or low dose (LCLB)-gel showed a sustained and controlled intra-articular release in both inflamed and healthy joints together with very low systemic exposure. Synovitis and lameness were moderate respectively very mild in this model due to the low concentration LPS (0.25 ng/joint). Both celecoxib formulations had a mild, transient effect on inflammatory and structural synovial fluid biomarkers but these returned to baseline within one week of administration. The HCLB-gel showed a significant inhibition in peak white blood cell concentration at 8 h after LPS induction. Elevated levels of celecoxib were observed in the joint for up to 30 days but no overall anti-inflammatory effects could be observed, which was thought to be due to the moderate synovitis. As there were no long-term adverse effects, sustained intra-articular release of celecoxib from in situ forming hydrogels should be evaluated further for its effects on longer-term relief of inflammatory joint pain in humans and animals.
Copyright © 2018 Elsevier B.V. All rights reserved.
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Publication Date: 2018-05-03 PubMed ID: 29729412DOI: 10.1016/j.ejpb.2018.05.001Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article presents a study on the sustained release of celecoxib, a non-steroidal anti-inflammatory drug (NSAID), specifically within the joint space using an in situ forming hydrogel, for treating synovial inflammation commonly found in arthritic disorders like osteoarthritis and rheumatoid arthritis.

Research Objectives and Methodology

The core aim of the researchers was to develop an effective treatment for joint inflammation by administering celecoxib directly into the joint. The researchers incorporated celecoxib into a propyl-capped PCLA-PEG-PCLA triblock copolymer hydrogel and injected it directly into the joint space.

  • The primary focus was to reduce undesirable systemic side effects associated with oral administration while maintaining effective concentrations of the drug in the joint space.
  • The researchers used an equine model with repeated lipopolysaccharide (LPS) induced synovitis to evaluate the effect of two different concentrations of celecoxib (40 mg/g and 120 mg/g).
  • The intra-articular release of the drug, systemic exposure to celecoxib and local changes at the joint level were measured over a period of time.

Research Findings

The findings from the study showed that a single injection of the high dose (HCLB)-gel or low dose (LCLB)-gel resulted in a regulated and sustained release of celecoxib within the joint, with minimal systemic exposure.

  • The induced synovitis and lameness in the model were moderate and very mild respectively due to the low LPS concentration used.
  • Both celecoxib formulations resulted in a mild, transient effect on the inflammatory and structural biomarkers in the synovial fluid, which returned to baseline within a week.
  • The higher concentration celecoxib formulation significantly inhibited the peak white blood cell concentration 8 hours after LPS induction, indicating a reduction in the inflammation response.
  • Elevated levels of the celecoxib drug were observed in the joint for up to 30 days, although no overall anti-inflammatory effects were observed, possibly due to the moderate synovitis induced in this model.

Implications and Conclusions

The researchers concluded that despite not observing an overall anti-inflammatory effect in the equine model, the sustained release of celecoxib from within the joint using in situ forming hydrogels could still have potential therapeutic benefits.

  • This method may have advantages in terms of reducing systemic side effects and prolonging drug retention in the joint, which could potentially provide longer-term relief from inflammatory joint pain in human and animal patients.
  • However, further evaluation and research are recommended before any conclusive benefits can be established.

Cite This Article

APA
Cokelaere SM, Plomp SGM, de Boef E, de Leeuw M, Bool S, van de Lest CHA, van Weeren PR, Korthagen NM. (2018). Sustained intra-articular release of celecoxib in an equine repeated LPS synovitis model. Eur J Pharm Biopharm, 128, 327-336. https://doi.org/10.1016/j.ejpb.2018.05.001

Publication

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
ISSN: 1873-3441
NlmUniqueID: 9109778
Country: Netherlands
Language: English
Volume: 128
Pages: 327-336
PII: S0939-6411(17)30988-8

Researcher Affiliations

Cokelaere, Stefan M
  • Dept. Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 112, 3584 CM Utrecht, The Netherlands. Electronic address: S.M.Cokelaere@uu.nl.
Plomp, Saskia G M
  • Dept. Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 112, 3584 CM Utrecht, The Netherlands; Department of Orthopaedics, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
de Boef, Esther
  • InGell Labs BV, L.J. Zielstraweg 1, 9713 GX Groningen, The Netherlands.
de Leeuw, Mike
  • InGell Labs BV, L.J. Zielstraweg 1, 9713 GX Groningen, The Netherlands.
Bool, Sophie
  • Dept. Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 112, 3584 CM Utrecht, The Netherlands.
van de Lest, Chris H A
  • Dept. Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 112, 3584 CM Utrecht, The Netherlands; Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 2, 3584 CM Utrecht, The Netherlands.
van Weeren, P René
  • Dept. Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 112, 3584 CM Utrecht, The Netherlands.
Korthagen, Nicoline M
  • Dept. Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 112, 3584 CM Utrecht, The Netherlands; Department of Orthopaedics, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.

MeSH Terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Biomarkers / analysis
  • Celecoxib / administration & dosage
  • Delayed-Action Preparations / administration & dosage
  • Disease Models, Animal
  • Female
  • Horses
  • Humans
  • Hydrogels / administration & dosage
  • Injections, Intra-Articular
  • Lipopolysaccharides / immunology
  • Male
  • Polyesters
  • Polyethylene Glycols
  • Synovial Fluid / chemistry
  • Synovitis / drug therapy
  • Synovitis / immunology

Citations

This article has been cited 22 times.
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