Field-induced pores formation during iontophoresis

离子电渗疗法过程中场诱导的孔隙形成

• 批准号: 6414420
• 负责人: Jagdish Singh
• 金额: $ 7.05万
• 依托单位: NORTH DAKOTA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6414420
• 关键词: atomic force microscopy; electric field; electrical conductance; electrolytes; human tissue; iontophoresis therapy; morphology; morphometry; skin; transdermal drug delivery

DESCRIPTION (provided by applicant): The long-term objective of the proposed research is to understand the mechanism of alteration in skin barrier properties by iontophoresis in order to develop transdermal drug delivery systems for macromolecules, including polypeptide hormones. Initiation of current flow across the skin causes a rapid decrease in resistance of the membrane to achieve a new lower value. Voltage-induced effects, which decrease the electrical resistance and proportionally increase the flux of both ionic permeants and polar, non-ionic solutes, suggest that these effects are primarily electric field induced pore formation. However, physical presence of electric field induced pores in the HSC has not been demonstrated. The overall hypothesis to be evaluated is that skin resistance changes are due to ions in the media changing the number of ions in the skin and formation of pores during iontophoresis. To test these hypotheses, we propose studies with the following Specific Aims: 1) To determine the effect of a constant D.C. voltage (200-10,000 mV), concentration, and type of electrolytes on the resistance (conductivity) of the HSC; 2a) To characterize topographical (structural) changes in the HSC in real time at sub-micrometer to nanometer levels using AFM; and 2b) to determine the number and size of field-induced pores per unit surface area during iontophoresis using AFM. We believe that the proposed research will significantly enhance our basic understanding about alterations in skin by iontophoresis for non-invasive delivery of macromolecules, including polypeptide hormones such as human growth hormone and insulin.

描述（由申请人提供）：拟议的长期目标 研究是了解皮肤屏障改变的机制 离子噬菌体的特性是为了开发透皮药物的递送 大分子的系统，包括多肽激素。 启动 流过皮肤的流动会导致电阻的迅速降低 膜以实现新的较低价值。 电压诱导的效果，这 降低电阻并按比例增加 离子渗透和极性溶质都表明这些影响 主要是电场诱导的孔形成。 但是，身体 尚未证明电场诱导的HSC中电场诱导的孔。 要评估的总体假设是皮肤耐药性的变化应归因于 介质中的离子改变了皮肤中离子的数量和形成 离子噬菌体期间的孔。 为了检验这些假设，我们建议 以下特定目的：1）确定恒定d.c的效果。 电压（200-10,000 mV），浓度和类型的电解质 HSC的电阻（电导率）； 2a）要表征地形 （结构性）HSC实时在亚微米中实时变化 使用AFM的水平；和2b）确定现场诱导的数量和大小 使用AFM在离子噬菌体期间，每单位表面积的孔。 我们相信 拟议的研究将大大增强我们对 通过离子噬菌体对皮肤的改变，无创递送 大分子，包括多肽激素，例如人类生长激素 和胰岛素。