Methods to Control Transdermal lontophoresis Variability

描述(由申请人提供)：该项目的目标是(1)从机械上量化传统恒流DC经皮离子导入过程中通量变化的原因，(2)克服这一问题，以便能够实现和保持恒定和精确的离子导入传输，用于不同疾病的治疗。常规恒流直流电经皮离子导入的受试者间和受试者内的可变性在文献中已被注意到，但尚未被提及。控制和保持恒定的经皮离子导入流量(即恒定的给药速率或恒定的提取速率)的重要性也在最近的离子导入进展中得到了证明。一个例子是用于管理糖尿病的新的非侵入性“反向”离子导入血糖监测系统。这项新技术可以改善糖尿病患者的生活质量，但存在流量不稳定的问题，导致平衡时间长，手指校准频繁。在治疗监测和治疗窗口狭窄的药物的系统给药中，对于从体内离子导入化合物的提取，通量的可变性给制药科学家带来了重大挑战，并限制了经皮离子导入给公众健康带来的潜在好处。在本项目中，我们建议检验这一假设，即通量的可变性是在离子导入过程中伴随着孔大小、孔电荷和/或孔路径改变的皮肤电阻变化的结果。我们还将测试一种新的恒定皮肤电阻方法，以克服这种通量可变性问题。该项目中获得的信息将帮助制药科学家更好地预测和控制全身给药和从体内提取化合物用于治疗、诊断和监测不同疾病的经皮离子导入通量。我们的结果还将促进对离子导入过程中皮肤通路的传输机制和屏障特性的了解，为未来加强离子导入传输的策略开发提供参考。

DESCRIPTION (provided by applicant): The objectives of this project are (1) to mechanistically quantify the causes of flux variability during conventional constant current DC transdermal iontophoresis and (2) to overcome this problem so constant and precise iontophoretic transport can be achieved and maintained for the treatment of different diseases. Inter-subject and intra-subject variability during conventional constant current direct current (DC) transdermal iontophoresis has been noted in the literature but has not been addressed. The importance of controlling and maintaining a constant transdermal iontophoretic flux (i.e., a constant drug administration rate or constant extraction rate) has also been demonstrated in recent iontophoresis advances. An example is the new non-invasive "reverse" iontophoresis blood glucose monitoring system for the management of diabetes. This new technology can improve the quality of life of diabetics but suffers from flux variability that results in long equilibration time and frequent finger-stick calibrations. For iontophoretic extraction of compounds from the body in therapeutic monitoring and systemic delivery of drugs having narrow therapeutic windows, flux variability has posed major challenges to pharmaceutical scientists and limited the potential benefit of what transdermal iontophoresis can bring to the health of the public. In the present project, we propose to test the hypothesis that flux variability is a result of the changes in skin electrical resistance accompanying pore size, pore charge, and/or pore pathway alterations during iontophoresis. We will also test a new constant skin electrical resistance approach to overcome this flux variability problem. The information obtained in this project will help pharmaceutical scientists better predict and control transdermal iontophoretic flux in systemic drug delivery and extraction of compounds from the body for the treatment, diagnosis, and monitoring of different diseases. Our results will also advance the knowledge of the transport mechanisms and the barrier properties of the skin pathways during iontophoresis for future strategy development to enhance iontophoretic transport.