TRANSDERMAL IONTOPHORESIS AND POLYPEPTIDES

这项建议寻求实施一种新颖的、系统的方法来研究 人体皮肤的离子导入传输特性。物理的影响- 化学因素，如分子大小和电荷的意思，离子 电解液的强度和pH值以及离子导入的方式(脉冲 相对于稳定的直流)的流量将是系统性的 采用四电极离子扩散池系统进行了研究。 离子导入输运理论模型的适用性， 结合这些物理化学因素对人体皮肤的影响 将受到严格的审查。这些研究将有助于更好地 从根本和更全面的角度理解离子导入 可控性透皮吸收治疗潜力的开发 输送小渗透剂。离子浮标和井的协同作用 阿司匹林经皮给药耐受化学尺寸限制 多肽。全面、机械地理解两者是如何 技术独立地和协同地影响着运输 皮肤对多肽的特性将被确定。体内研究 将进行一口井组合的可行性确定 耐受性化学渗透促进剂和离子导入 LHRH类似物亮丙瑞林经皮给药的全身效应 (抑制睾丸激素水平)。使用离子导入和 渗透增强器，用于通过提供 天然LHRH的周期性脉冲以获得所需的药理作用 对促黄体生成素和促卵泡刺激素分泌的影响也将被探索。

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.