Transdermal delivery enhanced by magainin pore-forming peptide
Transdermal delivery enhanced by magainin pore-forming peptide
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DOI：
10.1016/j.jconrel.2007.05.031
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发表时间：
2007-10-08
影响因子：
10.8
通讯作者：
Prausnitz, Mark R.
中科院分区：
文献类型：
--
作者：
Kim, Yeu-Chun;Ludovice, Peter J.;Prausnitz, Mark R.
在这项研究中，我们测试了一种假设，即magainin，一种在细菌细胞膜上形成毛孔的肽，可以通过破坏角质层脂质结构来增加皮肤的渗透性。我们进一步假设，镁镁素的增强需要与表面活性剂化学增强剂共同给药，以增加镁镁素对皮肤的渗透。为了支持这些假设，在50%乙醇溶液中暴露于已知的表面活性剂化学增强剂n -月桂醇肌氨酸（NLS），可使体外皮肤对荧光素的渗透性增加15倍，而magainin和NLS-乙醇的组合可协同提高皮肤渗透性47倍。相比之下，没有nls -乙醇的协同增强，皮肤渗透性不受暴露于magainin的影响。此外，共聚焦显微镜显示，在nls -乙醇的存在下，magainin深入而广泛地渗透到角质层，而单独的magainin进入皮肤的能力较差。傅里叶变换红外光谱、x射线衍射和差示扫描量热分析表明，nls -乙醇破坏了角质层的脂质结构，并且曼海兰蛋白和nls -乙醇的结合进一步破坏了角质层的脂质结构。综上所述，这些数据表明nls -乙醇增加了角质蛋白对角质层的渗透，进一步增加了角质层脂质破坏和皮肤渗透性。我们相信这是第一个证明使用成孔肽来增加皮肤渗透性的研究。本研究还提出了使用第一种化学增强剂来增加第二种化学增强剂对皮肤的渗透，从而协同增加皮肤对模型药物的渗透性的新概念。(C) 2007 Elsevier B.V.版权所有
In this study we tested the hypothesis that magainin, a peptide known to form pores in bacterial cell membranes, can increase skin penneability by disrupting stratum corneum lipid structure. We further hypothesized that magainin's enhancement requires co-administration with a surfactant chemical enhancer to increase magainin penetration into the skin. In support of these hypotheses, exposure to a known surfactant chemical enhancer, N-lauroyl sarcosine (NLS), in 50% ethanol solution increased in vitro skin permeability to fluorescein 15 fold and the combination of magainin and NLS-ethanol synergistically increased skin permeability 47 fold. In contrast, skin penneability was unaffected by exposure to magainin without co-enhancement by NLS-ethanol. Furthermore, confocal microscopy showed that magainin in the presence of NLS-ethanol penetrated deeply and extensively into stratum corneum, whereas magainin alone penetrated poorly into the skin. Additional analysis by Fourier-transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry showed that NLS-ethanol disrupted stratum corneum lipid structure and that the combination of magainin and NLS-ethanol disrupted stratum corneum lipids even further. Altogether, these data suggest that NLS-ethanol increased magainin penetration into stratum corneum, which further increased stratum corneum lipid disruption and skin permeability. We believe this is the first study to demonstrate the use of a pore-forming peptide to increase skin permeability. This study also presents the novel concept of using a first chemical enhancer to increase penetration of a second chemical enhancer into the skin to synergistically increase skin permeability to a model drug. (C) 2007 Elsevier B.V. All rights reserved.