Celecoxib for osteoarthritis

Puljak, Livia; Marı́n, A.; Vrdoljak, Davorka; Markotić, Filipa; Utrobičić, Ana; Tugwell, Peter

doi:10.1002/14651858.cd009865.pub2

Cited by 93 publications

(107 citation statements)

References 130 publications

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“…This inhibition decreases the recruitment of white blood cells and other inflammatory cells and decreases sensitization in pain receptors . Due to its COX‐2 selectivity, CXB has less gastrointestinal side effects than nonselective NSAIDs, sparing the gut mucosa and permitting its use for longer periods of time . The IA and IA + PO groups both exhibited similar trends of passive extension angle improvement throughout the remobilization period.…”

Section: Discussionmentioning

confidence: 96%

Inhibition of COX‐2 Pathway as a Potential Prophylaxis Against Arthrofibrogenesis in a Rabbit Model of Joint Contracture

Salib

Reina

Trousdale

et al. 2019

Journal Orthopaedic Research

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Arthrofibrosis is a common complication following total knee arthroplasty caused by pathologic fibroblast activation and excessive collagen deposition around a synovial joint leading to debilitating loss of motion. Treatment options are limited because the pathologic mechanisms remain to be characterized. Dysregulation of the inflammatory cascade may lead to communication between myofibroblasts and immune cells triggering tissue metaplasia, and excessive collagen deposition described clinically as arthrofibrosis. We explored the novel use of celecoxib (selective cyclooxygenase-2 [COX-2] inhibitor) to disrupt the downstream effects of the post-traumatic inflammatory cascade and inhibit scar tissue formation in a validated rabbit model of arthrofibrosis combined with new parameters for quantifying the stiffness of the posterior capsule. Biomechanical and molecular analyses, of contracted rabbit knee posterior capsule tissue after COX-2 inhibition revealed increased maximal passive extension and down-regulation of collagen messenger RNA compared with controls. Histopathologic examination suggested a trend of decreased quantities of dense fibrous connective tissue with COX-2 inhibition. These data may suggest that inhibiting the inflammatory cascade could potentially reduce pathologic myofibroblast activation, thereby reducing scar tissue formation and increasing the range of motion in arthrofibrotic joints. Implementing a multi-modal pharmacologic approach may simultaneously target numerous cellular components contributing to the complex process of arthrofibrogenesis.

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Section: Discussionmentioning

confidence: 96%

Inhibition of COX‐2 Pathway as a Potential Prophylaxis Against Arthrofibrogenesis in a Rabbit Model of Joint Contracture

Salib

Reina

Trousdale

et al. 2019

Journal Orthopaedic Research

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“…However, systemically administered NSAIDs suffer from poor distribution to joints and significant side effects including gastrointestinal problems and cardiovascular risks. For example, celecoxib (CXB) is an NSAID that was approved for use in OA treatment in the late 1990s . It is a potent cyclooxygenase‐2 inhibitor that blocks the production of prostaglandins and attenuates the inflammatory and pain responses that are associated with OA.…”

Section: Introductionmentioning

confidence: 99%

“…It is a potent cyclooxygenase‐2 inhibitor that blocks the production of prostaglandins and attenuates the inflammatory and pain responses that are associated with OA. However, its side effects have become apparent recently, and arise in part due to the high plasma concentrations required to provide relief from OA symptoms . The intra‐articular injection of the drug using a delivery system can potentially lead to a higher delivered dose while minimizing the side effects to off‐target tissues by reducing systemic drug levels …”

Section: Introductionmentioning

confidence: 99%

“…For example, celecoxib (CXB) is an NSAID that was approved for use in OA treatment in the late 1990s. 5 It is a potent cyclooxygenase-2 inhibitor that blocks the production of prostaglandins and attenuates the inflammatory and pain responses that are associated with OA. However, its side effects have become apparent recently, and arise in part due to the high plasma concentrations required to provide relief from OA symptoms.…”

Section: Introductionmentioning

confidence: 99%

“…However, its side effects have become apparent recently, and arise in part due to the high plasma concentrations required to provide relief from OA symptoms. 5,6 The intra-articular injection of the drug using a delivery system can potentially lead to a higher delivered dose while minimizing the side effects to off-target tissues by reducing systemic drug levels. 7 Several different classes of drug delivery systems have been studied for intra-articular use including hydrogels, 8 nanoparticles, 9,10 and crystalline drug formations.…”

Section: Introductionmentioning

confidence: 99%

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Poly(ester amide) particles for controlled delivery of celecoxib

Villamagna

Gordon

Hurtig

et al. 2019

J Biomedical Materials Res

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Many potential pharmacological treatments for osteoarthritis can result in undesirable side effects due to the systemic administration of drugs, making the direct delivery of drugs to joints an attractive alternative. Poly(ester amide)s (PEAs) have been shown to exhibit promising properties for the development of particle‐based intra‐articular delivery vehicles. However, a limited range of PEA structures has been investigated. In this study, we prepared and characterized the properties of two different PEA particles composed of l‐phenylalanine, sebacic acid, and either 1,4‐butanediol or 1,8‐octanediol (PBSe and POSe, respectively). The anti‐inflammatory drug celecoxib (CXB) was encapsulated into the particles. Despite minor structural differences, PBSe and POSe exhibited different thermal and mechanical properties, and encapsulation of CXB influenced these properties. PBSe‐CXB particles provided a slower release of drug in vitro relative to POSe‐CXB. Toxicity studies showed that particles without drug exhibited low toxicity to ATDC5 and C2C12 cells, while the PBSe‐CXB particles exhibited concentration‐dependent toxicity. Host response to the particles was evaluated in an ovine model. No adverse effects were observed following intra‐articular injection and it was observed that the particles diffused into the surrounding tissues. This work shows the importance of structural tuning in PEA delivery vehicles and demonstrates their potential for further development. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1235–1243, 2019.

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