Intra-articular treatment with triamcinolone acetonide-loaded liposomes in the rat high-fat diet groove model

Purpose:Local intra-articular injections with triamcinolone acetonide(TA) is favorable as an anti-inflammatory treatment. In animal (rat)models of OA it was shown that TA can reduce osteophyte formationand thus may be beneficial as a disease modifying treatment. To eval-uate the potential for slow-release anti-inflammatory treatment in amodel mimicking metabolically accelerated post-traumatic OA, weevaluated the effect of TA-loaded liposomes, in the high-fat diet groovemodel in rats.Methods:Thirty four male Wistar rats (Charles River) were fed a high-fat diet for 24 weeks where 60% of the kilocalories consist of fat(D12492i, 5.2kcal/g, Research Diets Inc., NJ, USA). In all animals, in bothknees, grooves were applied to the cartilage of both femur condyles, inweek 12. Then, in 1 week and 7 weeks post-surgery, they received anintra-articular injection with TA-loaded liposomes in their left knee.They received either 100 microgram (n¼17) or 30 microgram TA(n¼17). The right knee was used as a contralateral positive control andreceived either saline (n¼8) or empty liposomes (n¼26). To evaluatepain responses loading of the joints was monitored using a DynamicWeight Bearing (DWB) test setup (Bioseb, France). Micro-CT scans weremade using a Quantum FXm-CT scanner (PerkinElmer, MA, USA) atbaseline, pre-surgery and at the endpoint after 24 weeks.Results:An overall increase in weight was observed during the fulllength of the experiment for both treatment groups. However, after asingle intra-articular injection with liposomes containing 100 micro-gram TA , significant weight loss was observed for at least 7 days (figure1). After this period weight increased again and there was no significantdifference in weight at the end of the study between the high-dose andthe low-dose group. DWB showed a shift in weight towards the frontpaws and reduced rearing time shortly after surgery that normalizedafter treatment. But no difference between treatment groups wasobserved. MicroCT analysis showed significantly thinner lateral sub-chondral plate of the tibia at endpoint in the treated leg compared tothe untreated (sham treated) leg (figure2). Histological examinationshowed minor inflammation and no differences between treatments,controls or treated and untreated legs.Conclusions:Rats are particularly sensitive to corticosteroids as singleintra-articular injections with TA-loaded liposomes led to acute weightloss. This effect was previously observed with multiple (daily) injectionsof free TA, at the same concentration, suggesting the slow-release for-mulation is extremely potent. There was also an effect on lateral sub-chondral bone that was thinner in the treated legs compared tountreated legs. The TA-loaded liposomes seem to be tolerated well bythe joint and further evaluation in an OA model is recommended