Intra-articular Treatment of Osteoarthritis with Diclofenac-Conjugated
Polymer Reduces Inflammation and Pain
Version 2 2019-07-05, 15:50Version 2 2019-07-05, 15:50
Version 1 2019-07-03, 15:47Version 1 2019-07-03, 15:47
Posted on 2019-07-05 - 15:50
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
(C-DCF-PU) 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. In vitro 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 C-DCF-RH-PU 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 C-DCF-RH-PU 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.
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Sulistio, Adrian; Mansfeld, Friederike M.; Reyes-Ortega, Felisa; D’Souza, Asha M.; Ng, Sarah M. Y.; Birkett, Stephen; et al. (2019). Intra-articular Treatment of Osteoarthritis with Diclofenac-Conjugated
Polymer Reduces Inflammation and Pain. ACS Publications. Collection. https://doi.org/10.1021/acsabm.9b00232