Study of the Influence of the Penetration Enhancer Isopropyl Myristate on the Nanostructure of Stratum Corneum Lipid Model Membranes Using Neutron Diffraction and Deuterium Labelling

Study of the Influence of the Penetration Enhancer Isopropyl Myristate on the Nanostructure of Stratum Corneum Lipid Model Membranes Using Neutron Diffraction and Deuterium Labelling
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DOI:
10.1159/000338538
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发表时间:
2012-01-01
影响因子:
2.7
通讯作者:
Neubert, R. H. H.
Neubert, R. H. H.
中科院分区:
医学4区
文献类型:
--
作者:
Engelbrecht, T. N.;Deme, B.;Neubert, R. H. H.

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为了在分子水平上阐明亲脂性渗透促进剂肉豆蔻酸异丙酯 (IPM) 的作用模式,我们通过中子衍射研究了基于含有 10 wt% IPM 的神经酰胺 AP、胆固醇、棕榈酸和硫酸胆固醇的定向四元角质层 (SC) 脂质模型膜。我们的结果表明,IPM 在双层扰动和无序方面影响层状脂质组装。发生相分离,表明 IPM 由于其支链结构而不太可能与其他 SC 脂质正确混合。我们使用选择性氘标记来定位渗透增强剂,并成功证明了 IPM 在两个共存的层状相中的存在。我们得出的结论是,IPM 作为渗透促进剂的作用模式可能是基于掺入 SC 脂质基质、将某些 SC 脂质提取到单独的相中以及扰动多层脂质组装。版权所有 (C) 2012 S. Karger AG,巴塞尔
In order to elucidate the mode of action of the lipophilic penetration enhancer isopropyl myristate (IPM) on a molecular scale, we investigated oriented quaternary stratum corneum (SC) lipid model membranes based on ceramide AP, cholesterol, palmitic acid and cholesterol sulfate containing 10 wt% IPM by means of neutron diffraction. Our results indicate that IPM affects the lamellar lipid assembly in terms of bilayer perturbation and disordering. Phase segregation occurred, indicating that IPM is not likely to mix properly with the other SC lipids due to its branched structure. We used selective deuterium labelling to localize the penetration enhancer, and could successfully prove the presence of IPM in the two coexisting lamellar phases. We conclude that IPM's mode of action as penetration promoter is presumably based on incorporation into the SC lipid matrix, extraction of certain SC lipids into a separate phase and perturbation of the multilamellar lipid assembly. Copyright (C) 2012 S. Karger AG, Basel