Celecoxib-loaded PEA microspheres as an auto regulatory drug-delivery system after intra-articular injection

Janssen, M; Timur, Ufuk Tan; Woike, Nina; Welting, Tim J. M.; Draaisma, Guy; Gijbels, Marion J.J.; Rhijn, Lodewijk W. van; Mihov, George; Thies, Jens; Emans, Pieter J.

doi:10.1016/j.jconrel.2016.11.003

Cited by 67 publications

(64 citation statements)

References 45 publications

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“…A dose of 50 mg/animal was selected in order to have the most possible CXB injected into the joint, while maintaining the injectability of the drug delivery system. As reported by Janssen et al for different PEA particles, PBSe‐CXB particles appeared to have been engulfed by synovial lining cells and local macrophages, resulting in particles within the synovial villi . The mild increase in vascularity and intimal lining cells is consistent with the trauma of synovial fluid collection.…”

Section: Discussionsupporting

confidence: 77%

“…It is notable that the drug content of our particles was much higher than the 5 wt % CXB reported by Janssen et al in different PEA particles. 21 Higher drug content is desirable to minimize the dose of polymer required to administer a given quantity of drug.…”

Section: Discussionmentioning

confidence: 99%

“…Their thermal and mechanical properties as well as their degradation rates can be readily tuned through the incorporation of different monomers such as amino acids, diols, and dicarboxylic acids . PEAs have shown favorable properties as potential drug delivery systems when formulated as micelles or microparticles . They have also been shown to support the growth of cells and to exhibit good biocompatibility when studied in vivo .…”

Section: Introductionmentioning

confidence: 99%

“…17,18 PEAs have shown favorable properties as potential drug delivery systems when formulated as micelles 19 or microparticles. [20][21][22] They have also been shown to support the growth of cells [23][24][25] and to exhibit good biocompatibility when studied in vivo. 26,27 Thus far, there are very few examples involving the use of PEAs for intra-articular drug delivery.…”

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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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Poly(ester amide) particles for controlled delivery of celecoxib

Villamagna

Gordon

Hurtig

et al. 2019

J Biomedical Materials Res

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“…Also in a different, collagenase‐induced, rat model of OA, the extended release of TAA by PEA MSs did not show any effects on cartilage integrity nor induced tissue calcification (Rudnik‐Jansen et al, ). Given the absence of effects in previous studies of unloaded PEA MSs in OA animals, the MS platform per se is not likely to have contributed to the effects found either (Janssen et al, ; Rudnik‐Jansen et al, ), nor would have their combination with TAA bolus, given the absence of effects of either when administered separately. Together with the lack of effect of the bolus in OA animals and of TAA‐releasing PEA MSs in non‐operated healthy animals, our observations rather point towards an interaction of extended release of TAA with the pathological processes occurring in the ACLT + pMMx OA model.…”

Section: Discussionmentioning

confidence: 83%

Local controlled release of corticosteroids extends surgically induced joint instability by inhibiting tissue healing

Rudnik-Jansen

Tellegen

Pouran

et al. 2019

British J Pharmacology

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Background and PurposeCorticosteroids are intra‐articularly injected to relieve pain in joints with osteoarthritis (OA) or acute tissue damage such as ligament or tendon tears, despite its unverified contraindication in unstable joints. Biomaterial‐based sustained delivery may prolong reduction of inflammatory pain, while avoiding harmful peak drug concentrations.Experimental ApproachThe applicability of prolonged corticosteroid exposure was examined in a rat model of anterior cruciate ligament and medial meniscus transection (ACLT + pMMx) with ensuing degenerative changes.Key ResultsIntra‐articular injection of a bolus of the corticosteroid triamcinolone acetonide (TAA) resulted in enhanced joint instability in 50% of the joints, but neither instability‐induced OA cartilage degeneration, synovitis, nor the OA‐related bone phenotype was affected. However, biomaterial microsphere‐based extended TAA release enhanced instability in 94% of the animals and induced dystrophic calcification and exacerbation of cartilage degeneration. In healthy joints, injection with TAA releasing microspheres had no effect at all. In vitro, TAA inhibited cell migration out of joint tissue explants, suggesting inhibited tissue healing in vivo as mechanisms for enhanced instability and subsequent cartilage degeneration.Conclusions and ImplicationsWe conclude that short‐term TAA exposure has minor effects on surgically induced unstable joints, but its extended presence is detrimental by extending instability and associated joint degeneration through compromised healing. This supports a contraindication of prolonged corticosteroid exposure in tissue damage‐associated joint instability, but not of brief exposure.

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Research Progress on Injectable Microspheres as New Strategies for the Treatment of Osteoarthritis Through Promotion of Cartilage Repair

Lin,

Jia,

Cao

et al. 2024

Adv Funct Materials

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Osteoarthritis (OA) is a degenerative disease caused by a variety of factors with joint pain as the main symptom, including fibrosis, chapping, ulcers, and loss of cartilage. Traditional treatment can only delay the progression of OA, and classical delivery system have many side effects. In recent years, microspheres have shown great application prospects in the field of OA treatment. Microspheres can support cells, reproduce the natural tissue microenvironment in vitro and in vivo, and are an efficient delivery system for the release of drugs or biological agents, which can promote cell proliferation, migration, and differentiation. Thus, they have been widely used in cartilage repair and regeneration. In this review, preparation processes, basic materials, and functional characteristics of various microspheres commonly used in OA treatment are systematically reviewed. Then it is introduced surface modification strategies that can improve the biological properties of microspheres and discussed a series of applications of microsphere functionalized scaffolds in OA treatment. Finally, based on bibliometrics research, the research development, future potential, and possible research hotspots of microspheres in the field of OA therapy is systematically and dynamically evaluated. The comprehensive and systematic review will bring new understanding to the field of microsphere treatment of OA.

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Celecoxib-loaded PEA microspheres as an auto regulatory drug-delivery system after intra-articular injection

Cited by 67 publications

References 45 publications

Poly(ester amide) particles for controlled delivery of celecoxib

Poly(ester amide) particles for controlled delivery of celecoxib

Local controlled release of corticosteroids extends surgically induced joint instability by inhibiting tissue healing

Research Progress on Injectable Microspheres as New Strategies for the Treatment of Osteoarthritis Through Promotion of Cartilage Repair

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