In vitro evaluation of (S)-ibuprofen toxicity on joint cells and explants of cartilage and synovial membrane |
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Authors: | Laurent Bédouet Florentina Pascale Michel Bonneau Michel Wassef Alexandre Laurent |
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Institution: | aOcclugel, 24 rue du Faubourg Saint Jacques, 75015 Paris, France;bAP-HP, INRA, Center for Research of Interventional Imaging (CR2i), 78352 Jouy en Josas, France;cAP-HP Hôpital Lariboisière, Department of Pathology, University of Paris 7 – Denis Diderot, Faculty of Medicine, 2 rue Ambroise Paré, 75010 Paris, France;dAP-HP Hôpital Lariboisière, Department of Interventional Neuroradiology, 2 rue Ambroise Paré, 75475 Paris Cedex 10, France |
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Abstract: | Intra-articular drug delivery systems (DDSs) are envisaged as interesting alternative to locally release nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen to reduce pain in patients with osteoarthritis. The present study examines the toxicity of (S)-ibuprofen on chondrocytes and synoviocytes isolated from sheep shoulder joint and cultured in monolayers during 72 h, and on joint explants (cartilage and capsule) cultured in mono- or in co-culture for 13 days. (S)-ibuprofen (5 μM up to 1 mM) did not reduce the cell viability and protein content when added on chondrocyte monolayers, while at 1 mM (S)-ibuprofen reduced (by 8%, p = 0.01) the synoviocytes viability compared to untreated cells. During co-culture of joint explants, (S)-ibuprofen at 50 μM significantly reduced by 35% the spontaneous release of glycosaminoglycans (GAGs) from cartilage (p = 0.0065) whereas in monoculture, (S)-ibuprofen was inactive on GAG metabolism. (S)-ibuprofen at 1 mM significantly reduced cell lysis (lactate dehydrogenase leakage) by 74% during monoculture of capsule explants (p = 0.0136) and by 35% during co-culture of explants (p = 0.0013). Our findings demonstrate that the active isomer of ibuprofen at micro- and millimolar levels was not toxic for chondrocytes and synoviocytes and may reduce at 1 mM the cell lysis during culture of joint explants. The limited toxicity of (S)-ibuprofen at low and high concentration in sheep joint shoulder makes this enantiomer a promising drug candidate for the loading of intra-articular DDS. |
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Keywords: | Chondrocytes Co-culture Drug delivery systems Osteoarthritis (S)-ibuprofen Synoviocytes Toxicity |
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