Intra-articular treatment of osteoarthritis with diclofenac-conjugated polymer reduces inflammation and pain
| Autor: | Sarah M. Y. Ng, Andrew Craig Donohue, Adrian Sulistio, Cindy C. Shu, John F. Quinn, Stephen Lonsdale Birkett, Michael R. Whittaker, Thomas P. Davis, David Valade, Christopher B. Little, Anton Blencowe, Alison M. Bendele, Friederike M. Mansfeld, Asha M. D’Souza, Felisa Reyes-Ortega, Russell John Tait, Greg G. Qiao |
|---|---|
| Přispěvatelé: | Sulistio, Adrian, Mansfeld, Friederike M, Reyes-Ortega, Felisa, D'Souza, Asha M, Ng, Sarah MY, Birkett, Stephen, Blencowe, Anton, Qiao, Greg G, Little, Christopher B, Shu, Cindy C, Bendele, Alison M, Valade, David, Donohue, Andrew C, Quinn, John F, Whittaker, Michael R, Davis, Thomas P., Tait, Russell J. |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Drug
media_common.quotation_subject Biomedical Engineering Arthritis 02 engineering and technology Osteoarthritis Pharmacology Biomaterials 03 medical and health sciences Diclofenac Oral administration medicine local drug delivery 030304 developmental biology media_common intra-articular injection 0303 health sciences Biochemistry (medical) Chronic pain General Chemistry 021001 nanoscience & nanotechnology medicine.disease NSAID 3. Good health osteoarthritis controlled drug release polyurethane Drug delivery Implant 0210 nano-technology medicine.drug |
| Popis: | 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. Refereed/Peer-reviewed |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|