Methods to Control Transdermal lontophoresis Variability

控制经皮电渗疗法变异性的方法

• 批准号: 7176193
• 负责人: Kevin S. Li
• 金额: $ 20.46万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-01 至 2009-08-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7176193
• 关键词: Address; Applications Grants; Behavior; Blood Glucose; Body Fluids; Calibration; Cell Membrane Permeability; Charge; Chemicals; Classification; Condition; Databases; Development; Devices; Diagnosis; Disease; Drug Delivery Systems; Electrical Resistance; Electrolytes; Electrophoresis; Electroporation; Enhancers; Evaluation; Fingers; Frequencies; Future; Glucose; Goals; Human; Invasive; Investigation; Iontophoresis; Knowledge; Literature; Medical Dictionaries; Membrane; Methods; Modeling; Monitor; Movement; Numbers; Pathway interactions; Pharmacologic Substance; Principal Investigator; Property; Protocols documentation; Public Health; Quality of life; Rate; Relative (related person); Research; Resistance; Route; Sampling; Scientist; Site; Skin; System; Techniques; Technology; Testing; Therapeutic; Time; Transference; density; diabetes management; diabetic; drug administration rate; electric field; electrical potential; glucose monitor; improved; in vivo; migration; new technology; programs; size; theories; voltage

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.

该项目的目标是（1）机械地量化通量变化的原因 传统的恒流直流透皮离子导入疗法和（2）克服了这个问题所以恒流 可以实现并维持精确的离子电渗转运，以治疗不同的疾病。 传统恒流直流 (DC) 透皮治疗期间受试者间和受试者内的变异性 文献中已经提到了离子电渗疗法，但尚未得到解决。控制的重要性 并维持恒定的透皮离子电渗通量（即恒定的药物施用速率或 最近的离子电渗疗法的进展也证明了恒定的提取率。一个例子是 用于糖尿病管理的新型非侵入性“反向”离子电渗血糖监测系统。 这项新技术可以改善糖尿病患者的生活质量，但会受到通量变异性的影响，从而导致 平衡时间长和频繁的指尖校准。用于离子电渗法提取化合物 身体在治疗监测和全身输送药物时具有狭窄的治疗窗口、通量 变异性给制药科学家带来了重大挑战，并限制了药物的潜在益处 透皮离子导入疗法可以给大众带来健康。在本项目中，我们建议测试 假设通量变化是皮肤电阻随孔径变化而变化的结果， 离子电渗疗法期间的孔电荷和/或孔通路改变。我们还将测试新的常量皮肤 电阻方法可以克服这种通量变化问题。本次获得的信息 该项目将帮助制药科学家更好地预测和控制经皮离子导入通量 全身药物输送和从体内提取化合物用于治疗、诊断和 监测不同疾病。我们的结果还将增进对运输机制的了解 以及离子电渗疗法过程中皮肤通路的屏障特性，以供未来策略开发 增强离子电渗传输。