Iontophoresis of nafarelin across human skin in vitro.
Iontophoresis of nafarelin across human skin in vitro.
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那法瑞林在体外穿过人体皮肤的离子电渗疗法。
DOI：
10.1023/a:1016072205371
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发表时间：
1996
影响因子：
3.7
通讯作者：
Guy,RH
中科院分区：
文献类型：
--
作者：
RodríguezBayón,AM;Guy,RH
由于胃肠道中的蛋白水解酶和广泛的“首过”肝脏代谢，蛋白质和肽在口服给药后通常没有活性。然而，其他给药途径，包括透皮给药，提供了避免肝-胃肠道“首过”消除和更好的患者依从性的可能性（1）。由于肽和蛋白质具有大分子量，大多是亲水性的，并且通常是带电的，因此它们的被动透皮递送是不可能的，因此增强策略是必不可少的。离子电渗疗法，其采用一种钙离子电位梯度来驱动物质通过皮肤，代表了一种增加皮肤渗透性的方法（1-3）。那法瑞林是促黄体激素释放激素（LHRH）的十肽类似物。它是一种有效的超激动剂，对女性和男性都有几种生理作用（4，5）。已经证明了那法瑞林在人和无毛小鼠皮肤（hms）上的阳极离子电渗（6，7）。对通过hms的电转运的详细研究表明，增强递送的机制主要是通过电渗;然而，肽与皮肤的净负电荷强烈相关，有效地中和了这种性质，从而抑制了其自身的渗透（6-8）。已经表明，由于那法瑞林的阳极离子电渗作用，跨hms的电渗流（在正常的阳极到阴极方向上）可以减少十倍（8）。该效应取决于供体室中那法瑞林的浓度，随着浓度的增加变得更加重要（7）。
Due to proteolytic enzymes in the gastro—intestinal tract and extensive “first-pass” hepatic metabolism, proteins and peptides are not usually active following oral administration. However, other routes of drug delivery, including transdermal, provide the possibility of avoiding the hepato-gastrointestinal “first-pass” elimination and of better patient compliance (1). Because peptides and proteins have large molecular weights, are mostly hydrophilic and are often charged, their passive transdermal delivery is impossible, and an enhancement strategy is therefore essential. Iontophoresis, which employs an electri-cal potential gradient to drive substances through the skin, represents one approach to increase the skin’s permeability (1—3).Nafarelin is a decapeptide analog of leutinizing hormone releasing hormone (LHRH). It is a potent superagonist and has several physiological effects in both females and males (4, 5). The anodal iontophoresis of Nafarelin across both human and hairless mouse skin (hms) has been demonstrated (6, 7). Detailed study of its electrotransport through hms has revealed that the mechanism of enhanced delivery is primarily via electroosmosis; however, the peptide associates strongly with the skin’s net negative charge, effectively neutralizing this property, and thereby inhibiting its own permeation (6—8). It has been shown that electroosmotic flow across hms (in the normal anodal-to-cathodal direction) can be reduced by a factor of ten due to the anodal iontophoresis of Nafarelin (8). The effect is dependent upon the concentration of Nafarelin in the donor chamber, becoming more important with increasing concentration (7).