Zhang Xiuping, Shi Yang, Zhang Zhiyue, Yang Zhenlei, Huang Guihua
Department of Pharmaceutical Science, Shandong University, 44 Wenhua Xi Road, Ji'nan 250012, China.
Asian J Pharm Sci. 2018 May;13(3):229-238. doi: 10.1016/j.ajps.2017.12.007. Epub 2018 Jan 4.
Tetramethylpyrazine (TMP) is a traditional Chinese herbal medicine with strong anti-inflammatory and cartilage protection activities, and thus a promising candidate for treating osteoarthritis. However, TMP is rapidly cleared from the joint cavity after intra-articular injection and requires multiple injections to maintain efficacy. The aim of this study was to encapsulate TMP into poly (lactic-co-glycolic acid) (PLGA) microspheres to enhance the TMP retention in the joint, reducing injection frequencies and decreasing dosage. TMP microspheres were prepared by emulsion/solvent evaporation method. The intra-articular retention of the drug was assessed by detecting the drug concentration distributed in the joint tissue at different time points. The therapeutic effect of TMP microspheres was evaluated by the swelling of knee joints and histologic analysis in papain-induced OA rat model. The prepared freeze-dried microspheres with a particle size of about 10 µm can effectively prolong the retention time of the drug in the articular cavity to 30 d, which is 4.7 times that of the TMP solution. Intra-articular injection of TMP microspheres efficiently relieved inflammatory symptoms, improved joint lesions and decreased the depletion of proteoglycan. In conclusion, intra-articular injection of TMP loaded microspheres was a promising therapeutic method in the treatment of OA.
川芎嗪（TMP）是一种具有强大抗炎和软骨保护活性的传统中药，因此是治疗骨关节炎的一个有潜力的候选药物。然而，关节腔内注射后，TMP会迅速从关节腔清除，需要多次注射以维持疗效。本研究的目的是将TMP包裹于聚乳酸-羟基乙酸共聚物（PLGA）微球中，以提高TMP在关节内的保留时间，减少注射频率并降低剂量。通过乳液/溶剂蒸发法制备了TMP微球。通过检测不同时间点分布在关节组织中的药物浓度来评估药物在关节内的保留情况。在木瓜蛋白酶诱导的骨关节炎大鼠模型中，通过膝关节肿胀和组织学分析来评估TMP微球的治疗效果。制备的冻干微球粒径约为10μm，可有效将药物在关节腔内的保留时间延长至30天，是TMP溶液的4.7倍。关节腔内注射TMP微球可有效缓解炎症症状，改善关节损伤并减少蛋白聚糖的消耗。总之，关节腔内注射载TMP微球是治疗骨关节炎的一种有前景的治疗方法。
