Lee Hwankyu, Moon Hyungwon, Kim Hyun-Ryoung
Department of Chemical Engineering, Dankook University, Yongin-si 16890, Korea.
R&D Center, IMGT Co., Ltd., 172, Dolma-ro, Bundang-gu, Seongnam-si 13605, Korea.
Pharmaceutics. 2022 Jul 21;14(7):1512. doi: 10.3390/pharmaceutics14071512.
We perform coarse-grained molecular dynamics simulations of bilayers composed of various lipids and cholesterol at their different ratios. Simulations show that cholesterol-lipid interactions restrict the lateral dynamics of bilayers but also promote bilayer curvature, indicating that these opposite effects simultaneously occur and thus cannot significantly influence bilayer stability. In contrast, lyso-lipids effectively pack the vacancy in the bilayer composed of cone-shaped lipids and thus reduce bilayer dynamics and curvature, showing that bilayers are more significantly stabilized by lyso-lipids than by cholesterol, in agreement with experiments. In particular, the bilayer composed of cone-shaped lipids shows higher dynamics and curvature than does the bilayer composed of cylindrical-shaped lipids. To mimic ultrasound, a high external pressure was applied in the direction of bilayer normal, showing the formation of small pores that are surrounded by hydrophilic lipid headgroups, which can allow the release of drug molecules encapsulated into the liposome. These findings help to explain experimental observations regarding that liposomes are more significantly stabilized by lyso-lipids than by cholesterol, and that the liposome with cone-shaped lipids more effectively releases drug molecules upon applying ultrasound than does the liposome with cylindrical-shaped lipids.
我们对由不同比例的各种脂质和胆固醇组成的双层膜进行了粗粒度分子动力学模拟。模拟结果表明，胆固醇 - 脂质相互作用限制了双层膜的横向动力学，但同时也促进了双层膜的曲率，这表明这些相反的效应同时发生，因此不会对双层膜稳定性产生显著影响。相比之下，溶血磷脂有效地填充了由锥形脂质组成的双层膜中的空位，从而降低了双层膜的动力学和曲率，这表明与胆固醇相比，溶血磷脂对双层膜的稳定作用更为显著，这与实验结果一致。特别是，由锥形脂质组成的双层膜比由圆柱形脂质组成的双层膜表现出更高的动力学和曲率。为了模拟超声，在双层膜法线方向施加了高外部压力，结果显示形成了由亲水性脂质头部基团包围的小孔，这些小孔可以使包裹在脂质体中的药物分子释放出来。这些发现有助于解释关于溶血磷脂比胆固醇更能显著稳定脂质体，以及带有锥形脂质的脂质体在施加超声时比带有圆柱形脂质的脂质体更有效地释放药物分子的实验观察结果。
