MECHANISMS OF IONTOPHORETIC DRUG DELIVERY ACROSS SKIN

离子电渗疗法跨皮肤给药的机制

• 批准号: 3329504
• 负责人: RICHARD H GUY
• 金额: $ 21.87万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-08-01 至 1993-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3329504
• 关键词: drug delivery systems; electrophysiology; fluorescence microscopy; fluorescent dye /probe; iontophoresis therapy; laboratory mouse; skin absorption; synthetic peptide; topical drug application

The long-term objective of this research is to extend significantly the range of drugs for which transdermal delivery is a viable administration route. In particular, experiments are described to explore the potential of the skin as a systemic portal for new peptide and protein therapeutic agents emerging from the biotechnology industry. The focus of the proposal is to determine the feasibility and optimization of skin penetration enhancement by iontophoresis - the facilitation of (ionizable drug delivery across the skin by an applied electrical potential. The specific aims are to address the basic questions: By what mechanism(s) does iontophoresis enhance op iontophoresis dependent upon, and constrained by, penetrant properties? Iontophoresis concentrates attention on drug transport across the stratum corneum (SC, the outermost and least permeable skin layer) via "pores". The predominantly in vitro work proposed will: (a) use fluorescent probes and confocal microscopy to visualize routes of ionic flow across SC, (b) vectorize ionic transport with the vibrating probe electrode technique, (c) determine basic penetrant structure/properties-iontophoretic enhancement relationships, (d) develop the theoretical understanding of iontophoretic enhancement. Model penetrants for these experiments will be specifically designed peptide derivatives. Overall, a detailed examination of skin transport promotion by electrical means is outlined. In particular, the feasibility and optimization of peptide/small protein delivery, for which few acceptable alternatives exist, will be addressed.

这项研究的长期目标是显着扩展 透皮给药是一种可行的给药方式的一系列药物 路线。 特别是，描述了实验来探索潜力 皮肤作为新肽和蛋白质治疗的系统门户 生物技术行业新兴的代理商。 重点是 提案是确定皮肤的可行性和优化 通过离子电渗疗法增强渗透 - 促进（电离 通过施加电势将药物输送到皮肤上。 这 具体目标是解决基本问题：通过什么机制 离子电渗疗法是否增强离子电渗疗法取决于，以及 受渗透特性的限制吗？ 离子导入浓缩液 关注跨角质层（SC，最外层）的药物转运 和渗透性最低的皮肤层）通过“毛孔”。 主要是在体外 拟议的工作将：(a) 使用荧光探针和共焦显微镜 可视化跨 SC 的离子流路线，(b) 矢量化离子传输 使用振动探针电极技术，(c) 确定基本 渗透结构/性质-离子电渗增强关系， (d) 发展对离子电渗疗法增强的理论理解。 这些实验的渗透剂模型将专门设计 肽衍生物。 总体而言，对皮肤运输的详细检查 概述了通过电力手段进行的推广。 特别是可行性 以及肽/小蛋白递送的优化，对此很少有人 存在可接受的替代方案，并将予以解决。