Iontophoresis of monomeric insulin analogues in vitro: effects of insulin charge and skin pretreatment.
Iontophoresis of monomeric insulin analogues in vitro: effects of insulin charge and skin pretreatment.
复制标题
单体胰岛素类似物的体外离子电渗疗法：胰岛素电荷和皮肤预处理的影响。
DOI：
10.1016/s0168-3659(97)00155-7
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Guy,RH
中科院分区：
文献类型：
--
作者：
Langkjaer,L;Brange,J;Grodsky,GM;Guy,RH
本研究的目的是研究人胰岛素类似物的缔合状态和净电荷对跨无毛小鼠皮肤的离子电渗传输速率的影响，以及不同皮肤预处理对所述传输的影响。阳极输送时没有观察到胰岛素通量，可能是因为 Ag/AgCl 阳极的降解。对于人六聚胰岛素，通过完整皮肤的阴极离子电渗疗法期间的通量是微不足道的，并且对于单体胰岛素仅观察到低且可变的通量。另一方面，使用剥去的皮肤，带有两个额外负电荷的单体胰岛素的通量比六聚人胰岛素高 50-100 倍。引入三种额外电荷导致通量进一步增加 2-3 倍。在离子电渗疗法之前用无水酒精轻轻擦拭皮肤，相对于未经处理的皮肤，胰岛素的透皮转运增加了 1000 倍，即几乎与剥离皮肤的水平相同。酒精预处理降低了皮肤的电阻，大概是通过脂质提取。总之，具有至少两个额外负电荷的单体胰岛素类似物可以通过离子电渗疗法递送穿过无毛小鼠皮肤，而用人六聚胰岛素观察到微不足道的流量。在离子电渗疗法之前用无水酒精擦拭皮肤可以显着改善单体胰岛素的透皮转运，从而实现基础治疗的临床相关递送率。
The aim of this study was to investigate the influence of association state and net charge of human insulin analogues on the rate of iontophoretic transport across hairless mouse skin, and the effect of different skin pretreatments on said transport. No insulin flux was observed with anodal delivery probably because of degradation at the Ag/AgCl anode. The flux during cathodal iontophoresis through intact skin was insignificant for human hexameric insulin, and only low and variable fluxes were observed for monomeric insulins. Using stripped skin on the other hand, the fluxes of monomeric insulins with two extra negative charges were 50–100 times higher than that of hexameric human insulin. Introducing three additional charges led to a further 2–3-fold increase in flux. Wiping the skin gently with absolute alcohol prior to iontophoresis resulted in a 1000-fold increase in transdermal transport of insulin relative to that across untreated skin, i.e. to almost the same level as stripping the skin. The alcohol pretreatment reduced the electrical resistance of the skin, presumably by lipid extraction. In conclusion, monomeric insulin analogues with at least two extra negative charges can be iontophoretically delivered across hairless mouse skin, whereas insignificant flux is observed with human, hexameric insulin. Wiping the skin with absolute alcohol prior to iontophoresis gave substantially improved transdermal transport of monomeric insulins resulting in clinically relevant delivery rates for basal treatment.