Methods to Control Transdermal lontophoresis Variability

描述（由申请人提供）：本项目的目的是（1）从机械上量化传统恒流直流电经皮离子电渗疗法中通量变化的原因，以及（2）克服这一问题，以便实现并维持恒定和精确的离子电渗转运，用于治疗不同疾病。在文献中已经注意到常规恒流直流电（DC）经皮离子电渗期间的受试者间和受试者内变异性，但尚未得到解决。控制和维持恒定的经皮离子电渗通量（即，恒定的药物给药速率或恒定的提取速率）也已经在最近的离子电渗疗法进展中得到证实。一个例子是用于糖尿病管理的新的非侵入性“反向”离子电渗法血糖监测系统。这项新技术可以改善糖尿病患者的生活质量，但存在流量变化，导致平衡时间长和频繁的手指针刺校准。对于在治疗监测和具有窄治疗窗的药物的全身递送中从体内离子电渗提取化合物，通量变化性对药学科学家提出了重大挑战，并且限制了经皮离子电渗疗法可以为公众健康带来的潜在益处。在本项目中，我们建议测试的假设，即通量的变化是伴随着毛孔大小，毛孔电荷，和/或毛孔通路的改变在离子电渗的皮肤电阻的变化的结果。我们还将测试一种新的恒定皮肤电阻方法来克服这种通量变化问题。该项目获得的信息将帮助制药科学家更好地预测和控制全身药物输送和从体内提取化合物的经皮离子电渗通量，用于治疗，诊断和监测不同疾病。我们的研究结果也将推进知识的运输机制和屏障性能的皮肤途径在离子导入为未来的战略发展，以提高离子导入运输。

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.