TRANSDERMAL IONTOPHORESIS AND POLYPEPTIDES

透皮离子电渗疗法和多肽

• 批准号: 3302156
• 负责人: William I Higuchi
• 金额: $ 17.56万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-12-01 至 1993-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3302156
• 关键词: acidity /alkalinity; drug delivery systems; drug interactions; follicle stimulating hormone; hairless mouse; human tissue; ionic strengths; iontophoresis therapy; luteinizing hormone; membrane permeability; membrane potentials; molecular size; skin; testosterone

This proposal seeks to implement a novel, systematic approach to study the iontophoretic transport properties of human skin. The effect of physical- chemical factors such as molecular size and charge of the permeant, ionic strength and pH of the electrolyte and mode of iontophoresis (pulsed versus steady d.c) on the flux of the permeant will be systematically investigated using the four electrode iontophoretic diffusion cell system. The applicability of theoretical models of iontophoretic transport, incorporating the effect of these physical-chemical factors, to human skin will be critically examined. These studies will contribute to a better understanding of iontophoresis from a fundamental standpoint and a fuller exploitation of its therapeutic potential for the controlled transdermal delivery of small permeants. A synergism of iontophoreses and a well tolerated chemical size limitations to the transdermal delivery of polypeptides. A comprehensive, mechanistic understanding of how both technologies, separately and synergistically, influence the transport properties of skin to polypeptides will be established. In vivo studies will be conducted to establish the feasibility of a combination of a well tolerated chemical permeation enhancer and iontophoresis for the sustained transdermal delivery of leuprolide, a LHRH analog, for systemic effect (suppression of testosterone levels). Use of iontophoresis and a permeation enhancer to modulate the input characteristics by providing a periodic pulse of the native LHRH to elicit the desired pharmacological effect (stimulation of LH and FSH secretion) will also be explored.

该提案旨在实施一种新颖的、系统的方法来研究 人体皮肤的离子电渗传输特性。 物理效果—— 化学因素，例如分子大小和渗透物、离子的电荷 电解质的强度和 pH 值以及离子电渗疗法的模式（脉冲 与稳定的直流）对渗透物通量的影响将被系统地 使用四电极离子电渗扩散池系统进行研究。 离子电渗传输理论模型的适用性， 综合这些物理化学因素对人体皮肤的影响 将受到严格审查。 这些研究将有助于更好地 从基本的角度和更全面的角度理解离子电渗疗法 开发其在受控透皮疗法中的治疗潜力 输送小量渗透物。 离子电渗疗法和井的协同作用 经皮递送的耐受化学尺寸限制 多肽。 对两者如何进行全面、机械的理解 技术单独或协同地影响运输 将确定皮肤对多肽的特性。 体内研究 将进行以确定井组合的可行性 耐受的化学渗透增强剂和离子电渗疗法可持续 亮丙瑞林（一种 LHRH 类似物）的透皮给药，具有全身作用 （抑制睾酮水平）。 使用离子电渗疗法和 渗透增强剂通过提供调节输入特性 天然 LHRH 的周期性脉冲以引发所需的药理作用 效果（刺激 LH 和 FSH 分泌）也将被探索。