Temperature and pH sensitivity of a stabilized self-nanoemulsion formed using an ionizable lipid-like material via an oil-to-surfactant transition.
Temperature and pH sensitivity of a stabilized self-nanoemulsion formed using an ionizable lipid-like material via an oil-to-surfactant transition.
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使用可电离的类脂材料通过油到表面活性剂的转变形成稳定的自纳米乳液的温度和 pH 敏感性。
DOI：
10.1016/j.colsurfb.2016.11.020
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Akita H
中科院分区：
文献类型：
--
作者：
Tanaka H;Oasa S;Kinjo M;Tange K;Nakai Y;Harashima H;Akita H
以叔胺功能化的脂质（可电离脂质）具有ph依赖的正电荷，已被广泛开发为递送核酸的载体材料。我们之前开发了一种ss可切割的质子激活脂质样材料（ssPalm），作为包裹质粒DNA和短干扰RNA的纳米颗粒的功能化脂质包膜结构的组成部分。在这项研究中，我们报告了这种可电离脂质的独特特性：在没有货物（核酸）的情况下，通过ph触发的自乳化形成纳米级乳液（约40 nm）。该颗粒在生理pH值下具有中性电荷，并由辅助脂质和聚乙二醇（PEG）共轭脂质稳定。6-十二烷基-2-二甲氨基萘（Laurdan）的广义极化（表征水侵入表面引起的表面极性）随着pH和温度的变化而动态变化，而通过1,6-二苯基-1,3,5-己三烯（DPH）的荧光各向异性测量的颗粒内室的流动性不受影响。即使颗粒表面含有高密度的聚乙二醇，与传统的阳离子脂质相比，它在酸性pH值下对带负电荷的脂质体表现出高的融合性。这些特征表明ssPalm颗粒具有独特的特性，可以通过生物膜传递亲脂性药物。
Lipids functionalized with tertiary amines (ionizable lipids) for a pH-dependent positive charge have been developed extensively as a carrier material for delivering nucleic acids. We previously developed an SS-cleavable proton-activated lipid-like material (ssPalm) as a component of a functionalized lipid envelope structure of a nanoparticle that encapsulated plasmid DNA and short interfering RNA. In this study, we report on the unique characteristics of such an ionizable lipid: the formation of a nano-sized emulsion (ave. 40 nm) via pH-triggered self-emulsification in the absence of a cargo (nucleic acids). The particle has a neutral charge at physiological pH and is stabilized by helper lipids and polyethyleneglycol (PEG)-conjugated lipids. The generalized polarization of 6-dodecanoyl-2-dimethylaminonaphthalene (Laurdan), which indicates the surface polarity caused by the invasion of water onto the surface, changes dynamically in response to pH and temperature, while the fluidity of the intra-particle compartment, as measured by the fluorescence anisotropy of 1,6-Diphenyl-1,3,5-hexatriene (DPH), is not affected. Even when the particle contains a high density of PEG on the surface, it shows a high fusogenecity to negatively charged liposomes in response to an acidic pH to a higher degree than a conventional cationic lipid. These characteristics suggest that the ssPalm particle possesses unique properties for delivering lipophilic drugs across the biomembrane.