Li S K, Ghanem A H, Peck K D, Higuchi W I
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.
J Pharm Sci. 1999 Apr;88(4):419-27. doi: 10.1021/js980331y.
The present study aimed to investigate new pore induction as a flux-enhancing mechanism in human epidermal membrane (HEM) with low to moderate voltage electric fields. The extent of pore induction and the effective pore sizes of these induced pores were to be assessed using a low frequency (12.5 Hz) low to moderate voltage (2. 0 to 4.0 V) square-wave alternating current (ac) "passive" permeation method (ac iontophoresis). This ac approach was to allow for inducing and sustaining a state of pore induction in HEM while permitting no significant transport enhancement via electroosmosis; thus, transport enhancement entirely due to new pore induction (enhanced passive permeation) was to be assessed without any contributions from electroosmosis. Good proportionality between the increase in HEM permeability and its electrical conductance was found with the "passive" transport data obtained during square-wave ac iontophoresis using urea as the model permeant. Typically, at 3.0 to 4.0 V, HEM conductance increases (and permeability increases) ranged from around 3- to 30-fold. These results appear to be the first direct evidence that new pore induction in HEM is a significant flux enhancing mechanism under moderate voltage conditions. The extents of pore induction in HEM under low frequency moderate voltage (2.0 to 3.0 V) ac, pulsed direct current (dc), and continuous dc were also compared. The extents of pore induction from square-wave ac and pulsed dc were generally of the same order of magnitude but somewhat less than that observed during continuous dc iontophoresis at the same applied voltage and duration, suggesting less extent of pore induction with reversing polarity or when a brief delay is provided between pulses to allow for membrane depolarization. The average effective pore sizes calculated for the induced pores from the experimental data with urea and mannitol as probe permeants and the hindered transport theory were 12 +/- 2 A, which are of the same order of magnitude as those of preexisting pores determined from conventional passive diffusion experiments.
本研究旨在探讨在低至中等电压电场作用下，新孔诱导作为人表皮膜（HEM）通量增强机制的情况。将使用低频（12.5Hz）低至中等电压（2.0至4.0V）的方波交流电（ac）“被动”渗透方法（交流离子电渗疗法）来评估孔诱导的程度以及这些诱导孔的有效孔径。这种交流方法旨在允许在HEM中诱导并维持孔诱导状态，同时不通过电渗作用显著增强转运；因此，在没有电渗作用任何贡献的情况下，评估完全由于新孔诱导（增强的被动渗透）导致的转运增强。使用尿素作为模型渗透剂，在方波交流离子电渗疗法期间获得的“被动”转运数据表明，HEM通透性的增加与其电导率之间存在良好的比例关系。通常，在3.0至4.0V时，HEM电导率增加（以及通透性增加）范围约为3至30倍。这些结果似乎是首次直接证明在中等电压条件下，HEM中的新孔诱导是一种重要的通量增强机制。还比较了低频中等电压（2.0至3.0V）交流、脉冲直流电（dc）和连续直流电作用下HEM中的孔诱导程度。方波交流和脉冲直流电的孔诱导程度通常处于相同数量级，但略低于在相同施加电压和持续时间的连续直流电离子电渗疗法中观察到的程度，这表明在极性反转或在脉冲之间提供短暂延迟以允许膜去极化时，孔诱导程度较小。以尿素和甘露醇作为探针渗透剂，根据实验数据并利用受阻转运理论计算得出的诱导孔的平均有效孔径为12±2埃，与通过传统被动扩散实验确定的预先存在的孔的孔径处于相同数量级。
