Lee S H, Choi E H, Feingold K R, Jiang S, Ahn S K
Department of Dermatology, Yonsei University College of Medicine, Seoul, Korea.
J Invest Dermatol. 1998 Jul;111(1):39-43. doi: 10.1046/j.1523-1747.1998.00226.x.
Iontophoresis increases the delivery of drugs across the stratum corneum, but the pathway by which ionized drugs transit the stratum corneum is unknown. In this study we examined the effect of iontophoresis on the skin barrier and the epidermal calcium gradient. Hairless mice were subjected to iontophoresis for 5-120 min and skin specimens were prepared for electron microscopy. Neither positive nor negative iontophoresis affected transepidermal water loss. Lacunar dilatation and partial distention of the intercellular layers of the stratum corneum were observed in rough proportion to applied time in iontophoresis skin as well as control skin. Additionally, using calcium capture cytochemistry, we demonstrated that both positive and negative iontophoresis caused the disappearance of the epidermal calcium gradient with marked decrease in calcium content in the upper epidermis. Positive iontophoresis was associated with increased calcium in the stratum basale and dermis, whereas negative iontophoresis increased calcium in the stratum corneum. Moreover, as previously shown after barrier disruption and sonophoresis, the decrease in calcium content in the upper epidermis was associated with an increase in lamellar body secretion and the build up of lamellar material at the stratum corneum-stratum granulosum interface. In conclusion, iontophoresis on the skin of hairless mice may induce the change of ionized molecules in the epidermis, as the loss of the calcium gradient, which causes the decrease of skin impedence, gives charged drugs the ability to cross the skin more easily. Also, the structural changes, such as lacunar dilatation, whether they result from hydration or occlusion, may help the transport of charged drugs across the stratum corneum.
离子导入可增加药物透过角质层的递送量，但离子化药物穿过角质层的途径尚不清楚。在本研究中，我们检测了离子导入对皮肤屏障和表皮钙梯度的影响。对无毛小鼠进行5 - 120分钟的离子导入，然后制备皮肤标本用于电子显微镜检查。无论是正离子导入还是负离子导入均未影响经表皮水分流失。在离子导入皮肤以及对照皮肤中，角质层细胞间层的腔隙扩张和部分膨胀与施加时间大致成比例。此外，使用钙捕获细胞化学方法，我们证明正离子导入和负离子导入均导致表皮钙梯度消失，且表皮上层的钙含量显著降低。正离子导入与基底层和真皮中的钙增加有关，而负离子导入使角质层中的钙增加。此外，如先前在屏障破坏和超声导入后所显示的，表皮上层钙含量的降低与板层小体分泌增加以及角质层 - 颗粒层界面处板层物质的积累有关。总之，对无毛小鼠皮肤进行离子导入可能会诱导表皮中离子化分子的变化，因为钙梯度的丧失导致皮肤阻抗降低，使带电药物更容易穿过皮肤。而且，诸如腔隙扩张等结构变化，无论其是由水合作用还是闭塞引起的，都可能有助于带电药物穿过角质层。
