关节腔注射用甲氨蝶呤温敏凝胶的药效学及体内滞留性评价

发布时间：2018-10-25 17:48

【摘要】：目的:制备关节腔注射用甲氨蝶呤(methotrexate,MTX)温敏凝胶,并研究其在大鼠炎症模型中的治疗效果及体内滞留性。方法:以物理混合法制备甲氨蝶呤温敏凝胶,27只健康的SD大鼠随机分为3组,于皮下囊内注射含青霉素钠的羧甲基纤维素钠和脂多糖溶液建立类风湿关节炎模型,并分别注射生理盐水、MTX溶液及MTX温敏凝胶,并于给药后d 3,d 6,d 9采用酶联免疫吸附法检测各组大鼠渗出液中肿瘤坏死因子水平,同时取皮下囊皮肤制组织切片观察。将6只健康的小鼠随机分为2组后,分别经小鼠皮下囊注射混有近红外染料新吲哚菁绿的MTX溶液和MTX凝胶后,定时观察皮下囊处的荧光强度,考察载体的局部滞留性。结果:给药后d 3,MTX溶液组和MTX凝胶组的肿瘤坏死因子水平与生理盐水组相比分别下调了(27.31±4.37)%和(24.28±3.05)%;给药后d 6,2组分别下调了(42.70±3.92)%和(52.45±3.22)%;给药后d 9 2组分别下调了(52.28±4.00)%和(68.96±2.85)%。组织切片显示,MTX溶液组和MTX凝胶组相对生理盐水组炎症均有改善,而MTX凝胶组在给药后9 d时炎性细胞仍保持在较低水平,与溶液组具有显著性差异。在滞留性考察中,MTX溶液组在注射后1 d已基本消除,而MTX凝胶组在9 d时的滞留量为17.11%。结论:MTX温敏凝胶对该关节炎模型具有良好的治疗作用,且可增加药物在体内的滞留时间,长期治疗效果优于MTX溶液。
[Abstract]:Aim: to prepare methotrexate (methotrexate,MTX) thermosensitive gel for intraarticular injection and to study its therapeutic effect and retention in vivo. Methods: Methotrexate thermosensitive gel was prepared by physical mixing method. 27 healthy SD rats were randomly divided into 3 groups. The model of rheumatoid arthritis was established by subcutaneous injection of carboxymethyl cellulose sodium containing penicillin sodium and lipopolysaccharide solution. Physiological saline, MTX solution and MTX thermo-sensitive gel were injected respectively. The levels of tumor necrosis factor in the exudate of rats in each group were detected by enzyme-linked immunosorbent assay (Elisa) on day 3, day 6 and day 9, respectively. Six healthy mice were randomly divided into two groups. After subcutaneous injection of MTX solution and MTX gel mixed with neo indocyanine green, the fluorescence intensity of the subcutaneous capsule was observed and the local retention of the carrier was investigated. Results: the levels of tumor necrosis factor in MTX solution group and MTX gel group were decreased by (27.31 卤4.37)% and (24.28 卤3.05)%, (42.70 卤3.92)% and (52.45 卤3.22)%, respectively, and (52.28 卤4.00)% and (68.96 卤2.85)%, respectively. Tissue sections showed that the inflammation of MTX solution group and MTX gel group were improved compared with normal saline group, while the inflammatory cells in MTX gel group remained at a low level at 9 days after administration, which was significantly different from that in solution group. In the retention test, the retention of MTX solution group was basically eliminated 1 day after injection, while that of MTX gel group was 17.11 at 9 days. Conclusion: MTX thermo-sensitive gel has a good therapeutic effect on the arthritis model and can increase the retention time of the drug in vivo. The long-term therapeutic effect is better than that of MTX solution.
【作者单位】：广州军区武汉总医院;湖北中医药大学;
【分类号】：R965

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