發(fā)布時(shí)間：2018-10-25 17:48

【摘要】：目的:制備關(guān)節(jié)腔注射用甲氨蝶呤(methotrexate,MTX)溫敏凝膠,并研究其在大鼠炎癥模型中的治療效果及體內(nèi)滯留性。方法:以物理混合法制備甲氨蝶呤溫敏凝膠,27只健康的SD大鼠隨機(jī)分為3組,于皮下囊內(nèi)注射含青霉素鈉的羧甲基纖維素鈉和脂多糖溶液建立類(lèi)風(fēng)濕關(guān)節(jié)炎模型,并分別注射生理鹽水、MTX溶液及MTX溫敏凝膠,并于給藥后d 3,d 6,d 9采用酶聯(lián)免疫吸附法檢測(cè)各組大鼠滲出液中腫瘤壞死因子水平,同時(shí)取皮下囊皮膚制組織切片觀察。將6只健康的小鼠隨機(jī)分為2組后,分別經(jīng)小鼠皮下囊注射混有近紅外染料新吲哚菁綠的MTX溶液和MTX凝膠后,定時(shí)觀察皮下囊處的熒光強(qiáng)度,考察載體的局部滯留性。結(jié)果:給藥后d 3,MTX溶液組和MTX凝膠組的腫瘤壞死因子水平與生理鹽水組相比分別下調(diào)了(27.31±4.37)%和(24.28±3.05)%;給藥后d 6,2組分別下調(diào)了(42.70±3.92)%和(52.45±3.22)%;給藥后d 9 2組分別下調(diào)了(52.28±4.00)%和(68.96±2.85)%。組織切片顯示,MTX溶液組和MTX凝膠組相對(duì)生理鹽水組炎癥均有改善,而MTX凝膠組在給藥后9 d時(shí)炎性細(xì)胞仍保持在較低水平,與溶液組具有顯著性差異。在滯留性考察中,MTX溶液組在注射后1 d已基本消除,而MTX凝膠組在9 d時(shí)的滯留量為17.11%。結(jié)論:MTX溫敏凝膠對(duì)該關(guān)節(jié)炎模型具有良好的治療作用,且可增加藥物在體內(nèi)的滯留時(shí)間,長(zhǎng)期治療效果優(yōu)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 鹵4.37)% and (24.28 鹵3.05)%, (42.70 鹵3.92)% and (52.45 鹵3.22)%, respectively, and (52.28 鹵4.00)% and (68.96 鹵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.
【作者單位】： 廣州軍區(qū)武漢總醫(yī)院;湖北中醫(yī)藥大學(xué);
【分類(lèi)號(hào)】：R965

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