Sustained intra-articular release of celecoxib in an equine repeated LPS synovitis model.

Synovial inflammation is an important characteristic of arthritic disorders like osteoarthritis and rheumatoid arthritis. Orally administered non-steroidal anti-inflammatory drugs (NSAIDs) such as celecoxib are among the most widely prescribed drugs to manage these debilitating diseases. Intra-articular delivery in biodegradable in situ forming hydrogels overcomes adverse systemic effects and prolongs drug retention in the joint. In this study two formulations of celecoxib (40 mg/g and 120 mg/g) in a propyl-capped PCLA-PEG-PCLA triblock copolymer were sequentially evaluated in a multiple LPS challenge equine synovitis model. Intra-articular release and systemic exposure to celecoxib and local changes at joint level were evaluated longitudinally. A single intra-articular injection of the high dose (HCLB)-gel or low dose (LCLB)-gel showed a sustained and controlled intra-articular release in both inflamed and healthy joints together with very low systemic exposure. Synovitis and lameness were moderate respectively very mild in this model due to the low concentration LPS (0.25 ng/joint). Both celecoxib formulations had a mild, transient effect on inflammatory and structural synovial fluid biomarkers but these returned to baseline within one week of administration. The HCLB-gel showed a significant inhibition in peak white blood cell concentration at 8 h after LPS induction. Elevated levels of celecoxib were observed in the joint for up to 30 days but no overall anti-inflammatory effects could be observed, which was thought to be due to the moderate synovitis. As there were no long-term adverse effects, sustained intra-articular release of celecoxib from in situ forming hydrogels should be evaluated further for its effects on longer-term relief of inflammatory joint pain in humans and animals.

Functional locomotor consequences of uneven forefeet for trot symmetry in individual riding horses.

Left-right symmetrical distal limb conformation can be an important prerequisite for a successful performance, and it is often hypothesized that asymmetric or uneven feet are important enhancing factors for the development of lameness. On a population level, it has been demonstrated that uneven footed horses are retiring earlier from elite level competition, but the biomechanical consequences are not yet known. The objectives of this study were to compare the functional locomotor asymmetries of horses with uneven to those with even feet. Hoof kinetics and distal limb kinematics were collected from horses (n = 34) at trot. Dorsal hoof wall angle was used to classify horses as even or uneven (<1.5 and >1.5° difference between forefeet respectively) and individual feet as flat (<50°), medium (between 50° and 55°) or upright (>55°). Functional kinetic parameters were compared between even and uneven forefeet using MANOVA followed by ANOVA. The relative influences of differences in hoof angle between the forefeet and of absolute hoof angle on functional parameters were analysed using multiple regression analysis (P<0.05). In horses with uneven feet, the side with the flatter foot showed a significantly larger maximal horizontal braking and vertical ground reaction force, a larger vertical fetlock displacement and a suppler fetlock spring. The foot with a steeper hoof angle was linearly correlated with an earlier braking-propulsion transition. The conformational differences between both forefeet were more important for loading characteristics than the individual foot conformation of each individual horse. The differences in vertical force and braking force between uneven forefeet could imply either an asymmetrical loading pattern without a pathological component or a subclinical lameness as a result of a pathological development in the steeper foot.