MECHANISM OF DC AND PULSED IONTOPHORESIS

这项研究的长期目标是了解，在一个 机械水平，药物如何通过皮肤输送 同时在受控的环境中达到治疗性全身血液水平， 增强的方式。 方法和方式， 运输增强将调查是由应用程序 安全的低电压（离子电渗疗法）穿过被切除的人体， 裸鼠皮肤。 裸鼠皮肤将作为一种 筛选药物转运的替代临床前方法， 离子电渗疗法。 直流（恒定电流）和脉冲电流 将研究离子电渗药物递送的模式， 比较了 特别是，皮肤的离子传输选择性， 离子的运输途径，通过皮肤，效果增强 皮肤上的电荷传输，以及共同的影响， 施用离子电渗疗法和模型皮肤渗透性 将确定皮肤上的增强剂。 这些信息将 允许药物运输效率和组织改变效应 恒定电流和脉冲离子电渗疗法进行评估。 一个 最佳的离子电渗疗法输送协议，然后将开发 其最大化药物递送并最小化组织改变。 该方案将通过使用模型肽药物进行测试， 确定其通过人体皮肤的离子电渗运输。

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.