Formation of pH-Sensitive Cationic Liposomes from a Binary Mixture of Monoalkylated Primary Amine and Cholesterol
Formation of pH-Sensitive Cationic Liposomes from a Binary Mixture of Monoalkylated Primary Amine and Cholesterol
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DOI：
10.1021/la302278q
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发表时间：
2012-09-25
期刊：
影响因子：
3.9
通讯作者：
Lafleur, Michel
中科院分区：
文献类型：
--
作者：
Cui, Zhong-Kai;Bouisse, Anne;Lafleur, Michel
已有研究表明，单烷基两亲性化合物与甾醇的混合物可以形成液体有序(LO)层状相。这些双层膜可以用常规方法挤出，获得渗透性很低、对给定刺激有特定反应的大单层囊泡(LUV)。例如，pH的变化可以触发棕榈酸和甾醇形成的Luv的释放。本文研究了硬脂胺(SA)和胆固醇(CHOL)混合物形成非磷脂脂质体的可能性。用差示扫描量热法、红外光谱和氢核磁共振光谱对混合物的相行为进行了表征。结果表明，当体系的pH从5.5增加到12时，当体系从10相向固态转变时，这种特殊的混合物可以形成对pH敏感的层状相。随时间变化的释放实验表明，这些系统的渗透性相对较低。事实上，这些脂质体的稳定性依赖于pH，这意味着这些Luv作为一种新的阳离子载体显示出有趣的潜力，可以用于pH触发的释放。这是首次报道结合了总正电荷和pH敏感性的高甾醇含量的非磷脂脂质体。
It has been shown that mixtures of monoalkylated amphiphiles and sterols can form liquid-ordered (lo) lamellar phases. These bilayers can be extruded using conventional methods to obtain large unilamellar vesicles (LUVs) that have very low permeability and a specific response to a given stimulus. For example, pH variations can trigger the release from LUVs formed with palmitic acid and sterols. In the present work, the possibility to form non phospholipid liposomes with mixtures of stearylamine (SA) and cholesterol (Chol) was investigated. The phase behavior of these mixtures was characterized by differential scanning calorimetry, infrared, and H-2 NMR spectroscopy. It is found that this particular mixture can form a lo lamellar phase that is pH-sensitive as the system undergoes a transition from a lo phase to a solid state when pH is increased from 5.5 to 12. LUVs have been successfully extruded from equimolar SA/Chol mixtures. Release experiments as a function of time revealed the relatively low permeability of these systems. The fact that the stability of these liposomes is pH dependent implies that these LUVs display an interesting potential as new cationic carriers for pH-triggered release. This is the first report of non phospholipid liposomes with high sterol content combining an overall positive charge and pH-sensitivity.