电场方向对咖啡因电穿孔与离子导入经皮渗透的影响比较

Effect of Electric Field Direction on the Percutaneous Penetration of Caffeine Mediated by Skin Electroporation and Iontophoresis

目的研究电穿孔及离子导入时电场方向对分子型药物咖啡因经皮渗透的影响。方法采用双室扩散池方法,进行咖啡因饱和水溶液经人尸体皮肤被动扩散,电穿孔导入(指数衰减型脉冲,脉冲幅度为350 V,脉冲率为4次.m in-1,脉冲数为25,放电容量为22μF)、离子导入[0.25 mA.(cm2)-1,4 h]实验,考察电穿孔及离子导入对药物经皮渗透速率、累积经皮渗透量的影响,比较电穿孔与离子导入的促透作用。结果电穿孔与离子导入的咖啡因经皮渗透速率和累积渗透量均显著大于被动扩散。电场方向改变,电穿孔的促透作用无明显改变,离子导入的促透作用明显改变,正极离子导入的促透作用显著大于负极导入。在该实验条件下,外加脉冲的促透作用显著低于离子导入。结论与被动扩散相比,电穿孔和离子导入可显著增加分子型药物咖啡因的经皮渗透速率和累积渗透量。电场方向对电穿孔的促透作用无影响,而对离子导入的促透作用有明显影响。

Objective To study the effect of electric field direction on the pereutaneous penetration of the non-ionic drug caffeine mediated by skin electroporation and iontophoresis. Methods The percutaneous penetration of a saturated water solution of caffeine through the human cadaver skin by passive diffusion, electroporation （ exponentially decaying pulse, voltage = 350 V, pulse frequency = 4 pulses · min^-1 , pulse number = 25, capacity = 22 μF ） and iontophoresis [ 0.25 mA·（ cm^2 ）^-1 , 4- h] was studied with the two-chamber diffusion cell method in order to inspect the influences of electroporation and iontophoresis on the speed and cumulated amount of the drug through the skin. The effect of electric field direction on the enhanced percutaneous penetration of caffeine mediated by iontophoresis and electroporation was compared. Results The speed and cumulated amounts of caffeine through the skin mediated by electroporation and iontophoresis were both significantly greater than those by passive diffusion. The speed and cumulated amount of caffeine across the skin mediated by positive electroporation were similar to those by negative electroporation, while the speed and cumulated amount of the drug across the skin mediated by positive iontophoresis were significantly greater than those by negative iontophoresis. The enhancing effect of iontophoresis was greater than that of electroporation on the percutaneous penetration of caffeine in the present experiment. Conclusion In comparison with passive diffusion, electroporation and iontophoresis were shown to significantly increase the speed and cumulated amount of the non-ionic drug caffeine passing through the skin. The direction of electric field had no obvious influence on the enhancing effect of electroporation but had significant influence on the enhancing effect of iontophoresis.