title: In vitro evaluation of S-(+)-ibuprofen as drug candidate for intra-articular drug delivery system.
abstract: 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 µM and 1 mM. S-(+)-ibuprofen (50 µM) blocked prostaglandins production in LPS-activated explants but did not reduce cartilage degradation. By contrast, 1 mM 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 1 mM S-(+)-ibuprofen inhibited cartilage degradation via a mechanism independent of cyclooxygenase inhibition. Reduction of prostaglandins synthesis at 50 µM in all treatment groups and reduction of cartilage degradation observed at 1 mM suggest that S-(+)-ibuprofen could be considered as a promising drug candidate for the loading of intra-articular DDS.
authors.affiliation: Occlugel SAS, Jouy-en-Josas , France .
authors.forename: Laurent
authors.initials: L
authors.lastname: Bédouet
authors.forename: Florentina
authors.initials: F
authors.lastname: Pascale
authors.forename: Michel
authors.initials: M
authors.lastname: Bonneau
authors.forename: Alexandre
authors.initials: A
authors.lastname: Laurent
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D018920:Coculture Techniques / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007052:Ibuprofen / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D007270:Injections, Intra-Articular; D012756:Sheep; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007052:Ibuprofen
keywords: Cartilage; S-(+)-ibuprofen; co-culture; drug delivery systems; osteoarthritis