Transdermal delivery of peptides by iontophoresis.
Transdermal delivery of peptides by iontophoresis.
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通过离子电渗疗法透皮递送肽。
DOI：
10.1038/nbt1296-1710
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Guy,RH
中科院分区：
文献类型：
--
作者：
Hirvonen,J;Kalia,YN;Guy,RH
离子导入给药(利用外加电场的驱动力增强经皮肤的转运)已经被成功地证明，但肽序列/结构与给药效率之间的正式关系尚未建立。有一些值得注意的例子，例如亲脂性的亮氨酸释放激素(LHRH)类似物，那法瑞林和亮丙瑞林，它们在离子导入电流的影响下，自身在皮肤上的转运被下调。用LHRH寡肽验证了这种现象是由于这些阳离子多肽中和了皮肤的净负电荷所致。检测并量化了这些化合物对离子导入引起的溶剂进入皮肤的电渗流的影响，该电渗流对大的带正电荷的离子的电传输有显著贡献。阳离子残基和亲脂残基的紧密并列深刻地抑制了电渗透，并可能抑制了多肽的流动。结果表明，寡肽的亲脂性促进了范德华(Van Der Waals)与转运路线上疏水斑块的相互作用，从而允许带正电荷的寡肽与羧基侧链相互作用，从而在中性pH下给皮肤带来净负电荷。因此，亲脂性阳离子寡肽锚定在运输路径上，中和膜的原始电荷，并完全改变皮肤的渗透选择特性。
Transdermal administration by iontophoresis (enhanced transport via the skin using the driving force of an applied electric field) has been successfully demonstrated but no formal relationship between peptide sequence/structure and efficiency of delivery has been established. There are notable examples, such as the lipophilic leutinizing hormone releasing hormone (LHRH) analogs, Nafarelin and Leuprolide, that exhibit down-regulation of their own transport across the skin under the influence of an iontophoretic current. The hypothesis that this phenomenon is due to neutralization of the skin's net negative charge by these cationic peptides was examined with LHRH oligopeptides. The impact of these compounds on the electroosmotic flow of solvent into the skin, which is induced by iontophoresis and which contributes significantly to the electrotransport of large, positively charged ions, was examined and quantified. Close juxtaposition of cationic and lipophilic residues profoundly inhibited electroosmosis and, presumably, peptide flux. The results indicate that the lipophilicity of the oligopeptides facilitates van der Waals interactions with hydrophobic patches along the transport route, thereby permitting the positively charged oligopeptide to interact with carboxylate side chains that give the skin its net negative charge at neutral pH. The lipophilic, cationic oligopeptide, therefore, becomes anchored in the transport path, neutralizing the original charge of the membrane, and completely altering the permselective properties of the skin.