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Field-induced pores formation during iontophoresis

离子电渗疗法过程中场诱导的孔隙形成

基本信息

批准号：
6620281
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
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-04-01 至 2005-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6620281
关键词：
atomic force microscopy electric field electrical conductance electrolytes human tissue iontophoresis therapy morphology morphometry skin transdermal drug delivery

项目摘要

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的目的是了解皮肤屏障改变的机制为了开发透皮给药，大分子系统，包括多肽激素。开始流过皮肤的电流引起皮肤的电阻迅速减小，膜，以实现新的较低的值。电压诱导效应，降低电阻并按比例增加流量离子渗透物和极性非离子溶质都表明，主要是电场诱导的孔形成。但实物 HSC中电场诱导孔的存在尚未得到证实。待评估的总体假设是，皮肤电阻变化是由于改变皮肤中离子的数量，在离子电渗疗法期间的孔隙。为了验证这些假设，我们提出了以下研究：具体目的如下：1）确定恒定D.C. 电压（200- 10，000 mV）、浓度和电解质类型 HSC的电阻（电导率）; 2a）表征形貌 HSC在亚微米到纳米的真实的时间内的（结构）变化使用AFM的水平;和2b）确定场诱导的水平的数量和大小。使用AFM在离子电渗期间每单位表面积的孔隙。我们认为拟议的研究将大大提高我们对以下问题的基本认识：通过离子电渗疗法改变皮肤，大分子，包括多肽激素如人生长激素和胰岛素。