Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy & Drug Manufacturing, Pharos University in Alexandria (PUA), Alexandria, Egypt; Department of Pharmaceutics, Institute of Pharmacy, University of Bonn, Bonn, Germany.
Department of Pharmacology and Therapeutics, Faculty of Pharmacy & Drug Manufacturing, Pharos University in Alexandria (PUA), Alexandria, Egypt.
Int J Pharm. 2020 Jan 5;573:118859. doi: 10.1016/j.ijpharm.2019.118859. Epub 2019 Nov 25.
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.
骨关节炎（OA）的特征是退行性膝关节、手指和髋关节。在 OA 关节中，透明质酸（HA）的浓度和聚合发生变化；影响滑液的粘度。补充 HA 滑液含量，同时使用抗炎药物可能是一种具有成本效益的策略。由于游离药物在滑液中迅速清除，我们旨在制备用于关节内（IA）注射的原位形成凝胶的 Hyalomer。Hyalomer 包含泊洛沙姆 407（PX）作为热凝胶剂、HA 和双氯芬酸钾（DK）作为抗炎剂。根据溶胶-凝胶转变、凝胶时间、体外释放和 3 个月稳定性对 Hyalomer 配方进行了制备和表征。将选定的 Hyalomer 配方与各个成分一起IA 注射到 OA 大鼠模型中。优化的 Hyalomer 配方在 24 小时后释放 25%的 DK，在 4 天后释放 40%的 DK。凝胶时间为 40±2.08 s，凝胶温度为 26±1.87°C。Hyalomer 在 3 个月储存后保持药物释放百分比和 DK 含量。在 OA 大鼠中，Hyalomer 表现出最高的抗伤害和抗水肿作用。放射照相和组织病理学均显示 Hyalomer 治疗组再生的软骨轮廓。将 IA HA 和双氯芬酸结合在热响应凝胶中代表 OA 的一种有前途的治疗替代方案。
