Preliminary study focused on intra-articular drug administration

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonlyused for anti-inflammation and analgesia post-operatively inorthopaedic patients. Dexketoprofen trometamol is a water-solu-ble salt of the dextrorotatory enantiomer of non-steroidal anti-in-flamatory drug ketoprofen. The advantages of this productcompared with ketoprofen are faster onset of action, increasedpotency and possibly decreased potential for gastrointestinal sideeffects. Although it is found that chondrocytic cell proliferationand cell death are affected by certain non-selective NSAIDs andCOX-2 inhibitors, there is no available data about the effect ofdexketoprofen trometamol on chondrocytes.We hypothesized that intra-articular drug administration on post-operative pain could be a new therapeutic approach with limitedor any systemic side effects. For this purpose, initially, the cyto-toxic effects of the drug (ArvelesTM, dexketoprofen trometamol)on the chondrocytes were determinedin vitrousing mice primaryarticular chondrocyte culture. The culture of chondrocytes is oneof the most powerful tools for exploring the intracellular andmolecular features of chondrocytes. Several culture models haveproved useful for studying chondrocyte function, such as primarycultures of rabbit, bovine or rat chondrocytes. Cell lines fromchondrosarcoma produce larger numbers of cells but have tumori-genic properties that may fail to replicate physiological processes.The aim of the study is to evaluate the effects of ArvelesTM onmice primary articular chondrocyte culture. Therefore, chondro-cytes were isolated from articular cartilage obtained from kneesof 5–6 days old mice. Following the characterization of chondro-cytes, cytotoxic effects of the drug were determined using MTTtest. Primary cells were treated with drug for 15, 30, 45 and60 minutes exposure times at different concentrations. At the endof time intervals, including 24, 48 and 72 hours, primary mousechondrocytes were highly affected by all concentrations of drugtreatment compared to control groups.