氯诺昔康可溶性微针的制备及对类风湿性关节炎的药效学研究

Preparation of lornoxicam dissolving microneedles and pharmacodynamic studies on rheumatoid arthritis

目的:制备氯诺昔康可溶性微针贴片,并对其进行表征和抗类风湿性关节炎药效评价。方法:采用分步干燥法制备氯诺昔康可溶性微针(LN-DMNs),使用HPLC法测定其载药量,通过扫描电镜、皮内溶解试验、穿刺试验等方法检测微针的形态、稳定性、皮肤穿刺性能及恢复力;用Franz扩散池法对其体外渗透特性进行研究;药效学实验考察LN-DMNs对大鼠类风湿性关节炎的治疗作用。结果:所制备的微针排列整齐,针型较佳,平均载药量为(154.07±5.09)μg,具备较好的力学性能,能在大鼠皮肤留下明显孔洞。经微针治疗后,6 h内大鼠皮肤即可愈合至原来状态。体外透皮实验结果显示,LN-DMNs在36 h内累计渗透量为(78.39±1.15)μg·cm^(-2),药物累计透皮率达90.06%。药效学实验结果显示,LN-DMNs能够明显抑制类风湿性关节炎大鼠关节肿胀,显著降低血清中TNF-α、IL-1β含量、脾指数和胸腺指数(P<0.01),抑制滑膜炎症。结论:制备的LN-DMNs性能较佳,能够促进氯诺昔康的透皮递送,具有临床应用前景。

OBJECTIVE To prepare and characterize lornoxicam dissolving microneedle patches and evaluate its antirheumatoid arthritis efficacy.METHODS Lornoxicam dissolving microneedles(LN-DMNs)were prepared by stepwise drying method,and the drug loading was determined by HPLC.The morphology,stability,skin puncture performance and recovery per⁃formance of the prepared microneedles were respectively studied by scanning electron microscopy,intradermal dissolution test and puncture test.The transdermal properties were studied in vitro by the Franz diffusion cell method.Therapeutic effects of LNDMNs on rheumatoid arthritis in rats investigated by pharmacodynamic assays.RESULTS Microneedles were neatly arranged,the shape of the needles was good,the drug content of the whole piece was(154.07±5.09)μg,the needles had good mechanical properties and could leave obvious holes in rat skin.After treatment with the microneedles,the rat skin could be restored to the original condition within 6 hours.The cumulative penetration of LN-DMNs within 36 h was(78.39±1.15)μg·cm^(-2),and the cumulative penetration rate was 90.06%.The results of pharmacodynamic experiments showed that LN-DMNs could signifi⁃cantly inhibit joint swelling in rheumatoid arthritis rats,significantly reduce the serum levels of TNF-α,IL-1β,splenic index and thymic index(P<0.01)and suppress synovial inflammation.CONCLUSION The prepared LN-DMNs has good performance,and can promote the transdermal delivery of lonoxicam,which are promising for clinical application.