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The effect of a low transition temperature mixture for enhanced bioavailability of celecoxib in combination with hyaluronic acid in a rat model with post-traumatic knee osteoarthritis

2025-08Artigo científico Acesso aberto
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dc.contributor.authorRoda, Ana
dc.contributor.authorRios, Jaqueline Lourdes
dc.contributor.authorDilek, Yeter
dc.contributor.authorWarmink, Kelly
dc.contributor.authorEscudero, Remei
dc.contributor.authorMuenzebrock, Katrin A.
dc.contributor.authorDu, Jie
dc.contributor.authorWu, Zhiming
dc.contributor.authorEijkelkamp, Niels
dc.contributor.authorPaiva, Alexandre
dc.contributor.authorDuarte, Ana Rita C.
dc.contributor.authorCreemers, Laura B.
dc.contributor.institutionLAQV@REQUIMTE
dc.contributor.institutionFaculdade de Ciências e Tecnologia (FCT)
dc.contributor.institutionDQ - Departamento de Química
dc.contributor.pblElsevier
dc.date.accessioned2025-08-19T21:20:34Z
dc.date.available2025-08-19T21:20:34Z
dc.date.issued2025-08
dc.descriptionWe thank Saskia van Essen for helping with the histological staining. The authors thank Bloomage Biotechnology Corp., Ltd. for kindly providing the hyaluronic acid. by the European Union (ERC Consolidator Grant) from Horizon 2020 [ERC-2016-CoG 725034 Des.Solve]; and supported by the Associate Laboratory for Green Chemistry-LAQV, We also thank the funding agencies: Dutch Arthritis Association, LLP12; Turkish Government; Marie Sklodowska-Curie RESCUE CoFund GA801540 and CARTHAGO GA955335; China Scholarship Council. The funding bodies had no role in study design, data collection, data analysis, data interpretation and writing the manuscript. Publisher Copyright: © 2025 The Authors
dc.description.abstractOsteoarthritis (OA) is the most common form of arthritis and a leading cause of disability worldwide. Current therapies include pain relief with oral uptake of non-steroidal anti-inflammatory drugs (NSAIDs) and intra-articular injections of hyaluronic acid (HA), to restore the lubricant and protective properties of the joint (viscosupplementation). The administration of both therapies is limited, especially for NSAIDs, given the systemic side-effects. This work intended to explore the potential of a novel injectable gel for osteoarthritis treatment consisting of hyaluronic acid (HA) combined with celecoxib (CEX) incorporated in a glycerol:sorbitol (GS)-based Low Transition Temperature Mixture (LTTM) for enhanced bioavailability. The efficacy of HA+GS+CEX versus HA, HA+CEX and saline control was tested in a post-traumatic osteoarthritis rat model (female Sprague-Dawley rats, n = 6 per group), induced by unilateral anterior cruciate ligament transection and partial medial meniscectomy (ACLt+pMMx). Outcome measures included knee edema, pain-associated behaviour, systemic CEX levels, bone changes as detected by micro-computed tomography, joint degeneration by Mankin score and synovitis by Krenn score. No changes were observed in knee edema between treatments. All HA-containing formulations effectively reduced synovitis, and alleviated pain-associated behaviour. HA+GS+CEX injection limited the peak CEX systemic exposure, prevented the loss of integrity of the subchondral bone plate, and inhibited cartilage degeneration. Overall, although all HA-based formulations reduced pain and inflammation, only the combination of HA+GS+CEX inhibited joint degeneration, suggesting an added therapeutic benefit over HA or HA+CEX alone.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent3994054
dc.identifier.doi10.1016/j.biopha.2025.118239
dc.identifier.issn0753-3322
dc.identifier.otherPURE: 126487510
dc.identifier.otherPURE UUID: 67e87754-f429-449c-ae7e-25979f06b305
dc.identifier.otherScopus: 105008122716
dc.identifier.otherPubMed: 40527036
dc.identifier.otherORCID: /0000-0003-0800-0112/work/190141298
dc.identifier.urihttp://hdl.handle.net/10362/186640
dc.identifier.urlhttps://www.scopus.com/pages/publications/105008122716
dc.language.isoeng
dc.peerreviewedyes
dc.relationFunding Information: info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F50006%2F2020/PT
dc.relationinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F144424%2F2019/PT
dc.subjectCelecoxib
dc.subjectChondroprotective
dc.subjectHyaluronic acid
dc.subjectLow Transition Temperature Mixtures/Deep Eutectic Systems
dc.subjectNon-steroidal anti-inflammatory drugs
dc.subjectOsteoarthritis
dc.subjectPharmacology
dc.titleThe effect of a low transition temperature mixture for enhanced bioavailability of celecoxib in combination with hyaluronic acid in a rat model with post-traumatic knee osteoarthritisen
dc.typejournal article
degois.publication.titleBiomedicine and Pharmacotherapy
degois.publication.volume189
dspace.entity.typePublication
oaire.awardNumberSFRH/BD/144424/2019
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F144424%2F2019/PT
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccess
relation.isProjectOfPublication38ff01b4-3412-4f09-a002-b9fb7123d595
relation.isProjectOfPublication.latestForDiscovery38ff01b4-3412-4f09-a002-b9fb7123d595

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