MECHANISMS OF IONTOPHORETIC DRUG DELIVERY ACROSS SKIN

这项研究的长期目标是显著扩展 经皮给药可行的药物范围 路线。具体地说，描述了探索潜力的实验 皮肤作为新的多肽和蛋白质治疗的全身门户 从生物技术行业涌现的代理人。这次会议的重点是 建议是确定皮肤的可行性和最优化 离子导入增强渗透--促进(可电离的) 通过施加的电势通过皮肤输送药物。这个 具体目标是解决基本问题：通过什么机制(S) 离子导入是否增强了OP依赖的离子导入？ 受渗透性属性的限制？离子导入浓缩剂 关注药物通过角质层(SC，最外层)的转运 和最不透气的皮肤层)通过“毛孔”。以体外培养为主的 拟议的工作将：(A)使用荧光探头和共聚焦显微镜 可视化离子流经SC的路线，(B)将离子传输矢量化 用振动探头电极技术，(C)确定基本 渗透剂结构/性能-离子导入增强关系， (D)发展对离子导入增强的理论理解。 将专门设计用于这些实验的模型渗透剂 多肽衍生物。总体而言，对皮肤运输的详细检查 概述了通过电气手段进行的推广。尤其是它的可行性 和优化肽/小蛋白递送，对于较少的 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.