Field-induced pores formation during iontophoresis

简介(由申请人提供)：建议的长远目标 研究旨在了解皮肤屏障改变的机制 离子导入技术在药物透皮给药中的应用 大分子系统，包括多肽激素。发起 流经皮肤的电流导致皮肤的阻力迅速下降 膜实现了新的更低的价值。电压感应效应，它 降低电阻，并按比例增加磁通 离子渗透剂和极性、非离子溶质都表明，这些效应 主要是电场诱导的孔隙形成。然而，物理上 还没有证明HSC中存在电场诱导的气孔。 要评估的总体假设是，皮肤阻力的变化是 到介质中的离子改变皮肤中离子的数量和形成 离子导入过程中的毛孔。为了检验这些假设，我们提出了以下研究 具体目标如下：1)确定恒定直流的影响。 电压(200-10,000 mV)、浓度和电解液类型 用于表征地形的HSC的电阻(电导率；2a) (结构性)亚微米到纳米级的HSC实时变化 使用AFM的水平；以及2b)以确定场诱导的数量和大小 在使用原子力显微镜进行离子导入时，单位表面积上的孔数。我们相信 拟议的研究将极大地增强我们对 非侵入性给药的离子导入对皮肤的影响 大分子，包括多肽激素，如人生长激素 还有胰岛素。

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.