Phospholipid based vesicles called liposomes are commonly used as packaging in advanced drug delivery applications. Stimuli-responsive liposomes have been designed to release their contents under certain conditions, for example through heating or illumination. However, in the case of photosensitive liposomes based on azo-PC, namely phosphatidylcholine lipids with azobenzene incorporated into one of the two lipid tails, the release mechanism is not known. Here we show, using fully-atomistic molecular dynamics simulations of pure azo-PC bilayers, that drug permeation through the bilayer is driven by a light-induced gel-to-liquid lipid phase transition that softens the membrane bending rigidity by an order of magnitude, increases the area per lipid, and decreases the membrane thickness. Furthermore, using phenol as a model drug, we quantified its translocation free energy and its ability to cross the bilayer as a result of a chemical potential gradient induced through a double-bilayer simulation unit cell. The molecular level structural and dynamic information obtained in this study should be of help in designing new azo-PC based liposomes.

中文翻译：

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光开关 azo-PC 脂质双层的全原子分子动力学建模：结构、机械性能和药物渗透


基于磷脂的囊泡称为脂质体，通常用作高级药物递送应用中的包装。刺激响应脂质体被设计为在某些条件下释放其内容物，例如通过加热或照明。然而，在基于偶氮-PC 的光敏脂质体的情况下，即偶氮苯掺入两个脂质尾部之一的磷脂酰胆碱脂质，释放机制尚不清楚。在这里，我们使用纯 azo-PC 双层的全原子分子动力学模拟表明，药物通过双层的渗透是由光诱导的凝胶-液体脂质相变驱动的，该相变将膜弯曲刚度软化了一个数量级，增加了每种脂质的面积，并减小了膜厚度。此外，使用苯酚作为模型药物，我们量化了其易位自由能及其通过双层模拟晶胞诱导的化学势梯度穿过双层的能力。本研究中获得的分子水平结构和动力学信息应该有助于设计新的基于 azo-PC 的脂质体。