MECHANISMS OF IONTOPHORETIC DRUG DELIVERY ACROSS SKIN

这项研究的长期目标是显著延长 经皮给药是可行给药的药物范围 路线 特别是，实验描述了探索的潜力 皮肤作为新的肽和蛋白质治疗的系统门户 从生物技术产业中脱颖而出的代理商。 的重点 建议是确定皮肤的可行性和优化 通过离子电渗促进渗透-促进（可电离的 通过施加的电势将药物输送穿过皮肤。 的 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依赖于， 受渗透性能的约束 离子导入浓缩液 注意药物穿过角质层（SC，最外层）的转运 和最不渗透的皮肤层）。 主要在体外 拟议的工作将：（a）使用荧光探针和共聚焦显微镜， 可视化离子流穿过SC的路径，（B）使离子运输矢量化 用振动探针电极技术，（c）确定基本的 渗透剂结构/性能-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。 这些实验的模型转换器将专门设计 肽衍生物。 总的来说，皮肤运输的详细检查 概述了通过电子手段进行推广的情况。 特别是可行性 以及肽/小蛋白递送的优化， 存在可接受的替代方案，将予以解决。

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.