In vitro evaluation of S-(+)-ibuprofen as drug candidate for intra-articular drug delivery system
2015
Bédouet, Laurent | Pascale, Florentina | Bonneau, Michel, | Laurent, Alexandre,
Intra-articular drug delivery systems (DDSs) are envisaged as interesting alternative to locally release non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen to reduce pain in patients with osteoarthritis. The present study examines the efficacy of S-(+)-ibuprofen on cartilage degradation as drug candidate for DDS loading. Humeral cartilage and joint capsule explants were collected from healthy sheep shoulder joints and they were cultured in mono-or in co-culture for 13 days with LPS in combination with S-(+)-ibuprofen at 50 mu M and 1 mM. S-(+)-ibuprofen ( 50 mu M) blocked prostaglandins production in LPS-activated explants but did not reduce cartilage degradation. By contrast, 1mM S-(+)-ibuprofen treatment of cartilage explants reduced nitric oxide synthesis by 51% (p = 0.0072), proteoglycans degradation by 35% (p = 0.0114) and expression of serum amyloid protein -the main protein induced upon LPS challenge - by 44% (p<0.0001). On contrary, in presence of synovial membrane, the protective effects of S-(+)-ibuprofen on cartilage damages were significantly diminished. At 1mM, S-(+)-ibuprofen reduced the cell lysis during culture of cartilage and joint capsule either in mono-or in co-culture. This study performed on sheep explants shows that 1mM S-(+)-ibuprofen inhibited cartilage degradation via a mechanism independent of cyclooxygenase inhibition. Reduction of prostaglandins synthesis at 50 mu M in all treatment groups and reduction of cartilage degradation observed at 1mM suggest that S-(+)-ibuprofen could be considered as a promising drug candidate for the loading of intra-articular DDS.
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