Iontophoretic delivery across the skin: electroosmosis and its modulation by drug substances.
Iontophoretic delivery across the skin: electroosmosis and its modulation by drug substances.
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穿过皮肤的离子电渗传递：电渗及其药物的调节。
DOI：
10.1023/a:1012127512251
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发表时间：
1997
影响因子：
3.7
通讯作者：
Guy,RH
中科院分区：
文献类型：
--
作者：
Hirvonen,J;Guy,RH
目的.本研究的长期目标是了解离子电渗疗法的效率如何取决于给药药物的结构和理化性质。具体地，检查了某些药物种类改变皮肤的选择性渗透性质的能力。采用常规的体外方法，检测了5种不同亲脂性的β-受体阻滞剂对电渗流的抑制作用。最亲脂性的物种（普萘洛尔）和溶剂在阳极到阴极方向的对流运动的伴随电转运进行了测量。此外，还考虑了通过递送阴离子药物来增强电渗的可能性。亲脂性阳离子β-受体阻滞剂的离子电渗引起常规电渗的浓度依赖性抑制。最亲水的类似物没有引起任何影响。作为这种电荷中和现象的结果，普萘洛尔离子电渗的最佳浓度显著低于在水溶液中可达到的最大浓度。通过阴离子化合物的阴极离子电渗，仅引起对流溶剂流动的非常适度的改善。皮肤的选择透过性可以通过带正电荷并且具有显著的相邻疏水表面的药物来改变。后者似乎能够将分子“锚”在皮肤中，而膜的负电荷的反电荷确保了紧密的结合。亲脂性和正电荷都是必不可少的，没有这两者，就观察不到这种现象。然而，迄今为止研究的药物的构象灵活性，阻止了关于假定的“结合位点”的三维性质的明确结论。
Purpose. The long-term objective of this research is to understand how the efficiency of iontophoresis depends upon the structural and physicochemical properties of the administered drug. Specifically, the ability of certain drug species to alter the permselective properties of the skin was examined.Methods. Using conventionalin vitromethodology, the inhibition of electroosmotic flow induced by the iontophoresis of five different β-blockers (of varying lipophilicity) was examined. The concomitant electrotransport of the most lipophilic species (propranolol) and the convective movement of solvent in the anode-to-cathode direction were measured. In addition, the possibility that electroosmosis might be augmented by the delivery of anionic drugs was also considered.Results. Iontophoresis of lipophilic, cationic β-blockers caused a concentration-dependent inhibition of conventional electroosmosis. The most hydrophilic analogs elicited no effect. As a result of this charge neutralization phenomenon, the optimal concentration for propranolol iontophoresis was significantly less than the maximum achievable in aqueous solution. Only a very modest improvement in convective solvent flow was induced by the cathodal iontophoresis of anionic compounds.Conclusions. The permselectivity of the skin can be altered by drugs which are positively charged and which possess a significant, adjacent hydrophobic surface. The latter seems able to 'anchor' the molecule in the skin and the counter charge to the membrane's negative character ensures a tight association. Both lipophilicity and a positive charge are essential—without either, the phenomenon is not observed. The conformational flexibility of the drugs studied to-date, however, prevents unambiguous conclusions about the three-dimensional nature of the putative 'binding site'.