MECHANISM OF DC AND PULSED IONTOPHORESIS

这项研究的长期目标是了解 机械层面，药物是如何通过皮肤输送的 同时在受控的情况下实现治疗性全身血液水平 和增强的风度。使用的方法和方式 应用程序将对传输增强进行调查 安全的低电压(离子导入)在切除的人体和 裸鼠皮肤。裸鼠皮肤将被评估为 另一种筛选药物转运的临床前方法 离子导入。直流(恒流)和脉冲电流 将调查离子导入药物的给药方式，并 比较一下。特别是，皮肤的离子传输选择性， 离子通过皮肤的运输途径，增强了效果 皮肤上的电荷传输，以及CO-2的影响 离子导入给药与皮肤通透性模型 皮肤上的增强剂将被确定。此信息将 允许药物的传输效率和组织改变效果 恒流和脉冲离子导入的效果有待评估。一个 然后将开发最佳的离子导入方案 从而最大限度地增加药物输送，最大限度地减少组织改变。 该方案将通过使用一种模型多肽药物和 确定其在人体皮肤上的离子导入传输。

The long range objective of this research is to understand, on a mechanistic level, how drugs can be delivered through the skin while achieving therapeutic systemic blood levels in a controlled and enhanced manner. The method and manner by which transport enhancement will be investigated is by the application of a safe low voltage (iontophoresis) across excised human and nude mouse skin. The nude mouse skin will be evaluated as an alternative preclinical method for screening drug transport by iontophoresis. Both DC (constant current) and pulsed current modes of iontophoretic drug delivery will be investigated and compared. In particular, the skin's ion transport selectivity, the ion's transport pathway through the skin, the effects of enhanced charge transport on the skin, and the effects of the co- administration of iontophoresis and a model skin permeability enhancer on the skin will be determined. This information will allow the drug transport efficiencies and tissue alteration effects of constant current and pulsed iontophoresis to be assessed. An optimal iontophoretic delivery protocol will then be developed which maximizes drug delivery and minimizes tissue alteration. This protocol will be tested by using a model peptide drug and determining its iontophoretic transport across human skin.