TRANSDERMAL IONTOPHORESIS AND POLYPEPTIDES

该提案旨在采用一种新颖的系统方法来研究 人体皮肤的离子电渗传输特性。 物理的影响- 化学因素如渗透物的分子大小和电荷、离子 电解质的强度和pH以及离子电渗疗法的模式（脉冲 相对于稳态d.c）对渗透物通量的影响将系统地 研究使用四电极离子电渗扩散池系统。 离子电渗转运理论模型的适用性， 将这些物理化学因素的作用结合到人体皮肤上， 将被严格审查。 这些研究将有助于更好地 从基本观点和更全面的角度理解离子电渗疗法 开发其用于受控透皮给药的治疗潜力 小渗透物的递送。 离子电渗疗法和井的协同作用 对经皮递送的耐受化学尺寸限制 多肽。 一个全面的，机械的理解， 技术，单独和协同，影响运输 将确定皮肤对多肽的性质。 体内研究 将进行，以建立一个良好的组合的可行性， 耐受的化学渗透增强剂和离子电渗疗法， 亮丙瑞林（一种LHRH类似物）经皮给药的全身效应 （抑制睾丸激素水平）。 使用离子电渗疗法和 渗透增强剂，以通过提供 天然LHRH的周期性脉冲，以引起所需的药理学作用， 还将探索影响（刺激LH和FSH分泌）。

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.