Thermoresponsive Hyalomer intra-articular hydrogels improve monoiodoacetate-induced osteoarthritis in rats

Osteoarthritis (OA) is characterized by degenerative knees, fingers and hip joints. In OA joints, the concentration and polymerization of hyaluronic acid (HA) are changed; affecting the viscosity of the synovial fluid. Replenishing HA synovial fluid content, along with an anti-inflammatory drug could be a cost-effective strategy. As free drugs are rapidly cleared out of the synovial fluid, we aimed to prepare Hyalomer in situ forming gel for intra-articular (IA) injection. Hyalomer contains poloxamer 407 (PX) as thermogelling agent, HA, and diclofenac potassium (DK) as an anti-inflammatory. Hyalomer formulations were prepared and characterized in terms of sol-gel transition, gelation time, in vitro release and 3-month stability. The selected Hyalomer formula was injected IA in OA rat model, in comparison to its individual components. The optimized Hyalomer formulation showed 25% DK release after 24 h and 40% after 4 days. The gelation time was 40 ± 2.08 s and gelation temperature was 26 ± 1.87 °C. Hyalomer maintained the percentage drug release and DK content after 3-months storage. In OA rats, Hyalomer showed the highest anti-nociceptive and anti-edematous effect. Both radiography and histopathology revealed regenerated cartilage profile in Hyalomer-treated group. combining IA HA and diclofenac in thermoresponsive gel represents a promising therapeutic alternative for OA.