目的 在微针作用下,考察青藤碱水凝胶贴剂透皮给药的特点与规律。方法 制备不同长度的微针,并制备青藤碱水凝胶贴剂;离体小鼠皮肤经不同针形微针预处理相同时间、相同针形微针预处理不同时间后贴敷青藤碱水凝胶贴剂,用改进的Franz扩散池研究青藤碱的透过规律并与未处理皮肤的被动扩散进行比较;高效液相色谱法测定青藤碱的含量。结果 100μm微针、200μm微针预处理皮肤后青藤碱透皮速率分别是未经微针预处理的40.7、52.4倍;200μm微针预处理皮肤7 min后青藤碱的透皮速率是未经微针预处理的142.0倍。200μm微针经不同的力预处理后,青藤碱的透皮速率随着力的增大而增大,当力大于5 N时透皮速率趋于平衡。结论 微针与水凝胶贴剂结合经皮给药时,透皮速率显著提高,并且微针针形、预处理时间和所受的力对药物的经皮渗透具有重要影响。

Objective Using the effect of microneedle array to investigate the feature and rule of transdermal drug delivery of sinomenine hydrogel patch.Methods The microneedles with different length and sinomenine hydrogel patch were prepared;The isolated rat skin was pretreated by different needle-shapes of microneedle array and different timepoints with the same needle-shape,and then sticked the sinomenine patch.The permeation rates of sinomenine were studied using a Franz diffusion cell and compared with passive diffusion of the rat skin untreated.Sinomenine content was measured by HPLC.Results The permeation rates of sinomenine via the skin pretreated with 100 and 200 μm microneedles were 40.7 and 52.4 times to those of the untreated.The permeation rates of sinomenine via the skin pretreated 7 min with 200 μm microneedles is 142.0 times to those of the untreated.When skins were pretreated using 200 μm microneedles with different force, the drug permeation rates were increased with the force increasing.When the force exceeded 5 N,the drug permeation rates were equilibrium.Conclusion When transdermal drug delivery by using microneedle array-hydrogel patch,the permeation rates increase significantly.The needle-shape,skin pretreating time,and force of the microneedles play the important roles in the transdermal drug delivery.

陕西省中医管理局科研基金(200725-05)；西北大学研究生重点课程建设项目(08YKC25)；西北大学研究生创新基金资助项目(08YJC23)