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Papers of the Week

Papers: 15 Jan 2022 - 21 Jan 2022

Animal Studies

2019 Jul 15

ACS Appl Bio Mater



Intra-articular Treatment of Osteoarthritis with Diclofenac-Conjugated Polymer Reduces Inflammation and Pain.


Sulistio A, Mansfeld FM, Reyes-Ortega F, D'Souza AM, Ng SMY, Birkett S, Blencowe A, Qiao GG, Little CB, Shu CC, Bendele AM, Valade D, Donohue AC, Quinn JF, Whittaker MR, Davis TP, Tait RJ
ACS Appl Bio Mater. 2019 Jul 15; 2(7):2822-2832.
PMID: 35030816.


The most common treatment for osteoarthritis is daily oral administration of a nonsteroidal anti-inflammatory drug such as diclofenac. This daily dosage regime is often associated with severe side effects. In this study, we explored the potential of utilizing a high molecular weight cross-linked polyurethane polymer covalently linked to diclofenac () for intra-articular administration. We aim to exploit the advantages of local drug delivery by developing an implant with improved efficacy and reduced side effects. The polymer was synthesized from a diclofenac-functionalized monomer unit in a simple one-pot reaction, followed by cross-linking. drug release studies showed zero-order drug release for 4 days, followed by a gradual decline in drug release rate until diclofenac was depleted after 15 days. The cross-linked polymer was triturated to yield an injectable microgel formulation for administration. Whole animal fluorescence imaging of the rhodamine-labeled showed good retention of the polymer in the knee joints of healthy rats, with approximately 30% of the injected dose still present 2 weeks post intra-articular administration. In a reactivation arthritis animal model, the formulation reduced pain and significantly reduced inflammation after a short lag phase, showing that this drug delivery system warrants further development for long-term treatment of osteoarthritis with the benefit of reduced side effects.