Inada H, Ghanem A H, Higuchi W I
Department of Pharmaceutics, College of Pharmacy, University of Utah, Salt Lake City 84112.
Pharm Res. 1994 May;11(5):687-97. doi: 10.1023/a:1018924228916.
The effects of applied voltage and the duration of application upon human epidermal membrane (HEM) alterations and recovery were investigated. All experiments were conducted using a two-chamber diffusion cell with constant DC voltage (250-4000 mV) applied over a predetermined period, and HEM changes were monitored by measuring the electrical resistance before and after voltage termination. The key findings were that the rate of decrease in resistance was strongly dependent upon the applied voltage, the reversible recovery times were dependent upon both the magnitude and the duration of the applied field (frequently were several orders of magnitude greater than times for attaining significant resistance reduction), and reversible recovery times were much longer when lower voltages were applied for longer times to attain the same decrease in electrical resistance than for higher voltages at short times. These findings closely parallel those obtained on electrical breakdown/recovery of bilayer membranes (electroporation). The second part of this work examined the hypothesis that decreases in HEM electrical resistance induced by the applied voltage are accompanied by proportional increases in HEM permeability. A study was designed to test this hypothesis involving a four-stage protocol with HEM: passive transport, 250-mV iontophoresis, 2000-mV iontophoresis for 10 min, then back to 250-mV iontophoresis. The data obtained strongly support the view that the HEM alterations induced by the electric field result in pore formation and in the expected changes in HEM permeability.
研究了施加电压及施加持续时间对人表皮膜（HEM）变化和恢复的影响。所有实验均使用两室扩散池进行，在预定时间段内施加恒定直流电压（250 - 4000 mV），通过测量电压终止前后的电阻来监测HEM的变化。关键发现是，电阻下降速率强烈依赖于施加电压，可逆恢复时间既取决于施加电场的大小，也取决于施加持续时间（通常比达到显著电阻降低所需的时间大几个数量级），并且当以较低电压长时间施加以达到相同电阻降低时，可逆恢复时间比短时间施加较高电压时长得多。这些发现与双层膜电击穿/恢复（电穿孔）的结果非常相似。这项工作的第二部分检验了以下假设：施加电压引起的HEM电阻降低伴随着HEM通透性成比例增加。设计了一项研究来检验这一假设，该研究对HEM采用四阶段方案：被动转运、250 mV离子电渗疗法、2000 mV离子电渗疗法持续10分钟，然后回到250 mV离子电渗疗法。获得的数据有力地支持了以下观点：电场引起的HEM变化导致孔形成以及HEM通透性的预期变化。
