Characterization of intra-articular dose administration in the stifle joint of rabbits for toxicity testing

Intra-articular administration is a standard therapeutic option for patients with rheumatoid arthritis, and pharmaceutical companies are increasing the research and development of injectable treatments. Therefore, there is an unmet need for reliable dosing models in toxicity safety testing. The rabbit stifle joint is attractive for toxicology testing of injectable treatments for rheumatoid arthritis because it is the largest synovial joint in the animal's body and is equivalent in structure and function to the human knee. Intra-articular dosing in rabbits is one model currently being used in general toxicology studies to assess the safety of injectable compounds. In this study, intra-articular dose administration was characterized in the stifle joints of New Zealand white rabbits. An anesthesia regimen was developed for the intra-articular injection procedure. Volumes of ≤400 =L were successfully injected into the stifle joint of rabbits. Injection success was confirmed by visual inspection of contrasting agent within the articular space, with minimal leakage and no rupturing of the synovial membrane observed. A post-procedural analgesia regimen was developed to alleviate pain and discomfort. Bilateral and multiple injections were also explored and determined feasible. In addition, successful synovial fluid recovery without flushing was demonstrated. Histopathology of the stifle joint demonstrated that the injection procedure caused minimal inflammation or effects on the stifle joint or articular cartilage. In summary, intra-articular dose administration by injection to the stifle joint(s) of rabbits is a successful procedure for use in preclinical safety evaluation