Methods to Control Transdermal lontophoresis Variability

描述（由申请人提供）：本项目的目标是(1)机械地量化常规恒流直流透皮离子导入过程中通量变化的原因，(2)克服这一问题，从而实现并保持恒定和精确的离子导入传输，以治疗不同疾病。在传统的恒流直流电（DC）透皮离子导入过程中，受试者之间和受试者内部的变异已经在文献中被注意到，但尚未得到解决。在最近的离子透入进展中，控制和维持恒定的透皮离子透入通量（即恒定的给药速率或恒定的萃取速率）的重要性也得到了证明。一个例子是用于糖尿病管理的新型无创“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，但存在通量可变性，导致平衡时间长，手指棒校准频繁。对于从体内离子透入提取化合物用于治疗监测和具有狭窄治疗窗口的药物的全身递送，通量可变性对制药科学家提出了重大挑战，并限制了透皮离子透入给公众健康带来的潜在益处。在目前的项目中，我们建议测试通量可变性是离子导入过程中伴随着孔径、孔电荷和/或孔路径改变的皮肤电阻变化的结果的假设。我们还将测试一种新的恒定皮肤电阻方法来克服这种磁通可变性问题。在这个项目中获得的信息将帮助制药科学家更好地预测和控制透皮离子渗透通量在全身药物传递和提取化合物从体内的治疗，诊断和监测不同的疾病。我们的研究结果也将促进对离子透入过程中皮肤通路的传输机制和屏障特性的了解，为未来加强离子透入传输的策略开发提供依据。

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.