Hsu Ting-Wei, Yang Ching-Hsun, Su Chun-Jen, Huang Yin-Tzu, Yeh Yi-Qi, Liao Kuei-Fen, Lin Tien-Chang, Shih Orion, Lee Ming-Tao, Su An-Chung, Jeng U-Ser
National Synchrotron Radiation Research Center, 101 Hsin-Ann Road, Hsinchu Science Park, Hsinchu 300094, Taiwan.
Department of Chemical Engineering, National Tsing Hua University, Hsinchu 300044, Taiwan.
J Appl Crystallogr. 2023 Jul 25;56(Pt 4):988-993. doi: 10.1107/S1600576723005393. eCollection 2023 Aug 1.
Liposome development is of great interest owing to increasing requirements for efficient drug carriers. The structural features and thermal stability of such liposomes are crucial in drug transport and delivery. Reported here are the results of the structural characterization of PEGylated liposomes via small- and wide-angle X-ray scattering and an asymmetric flow field-flow fractionation (AF4) system coupled with differential refractive-index detection, multi-angle light scattering (MALS) and dynamic light scattering. This integrated analysis of the exemplar PEGylated liposome formed from hydrogenated soy phosphatid-yl-choline (HSPC) with the addition of cholesterol reveals an average hydro-dynamic radius ( ) of 52 nm with 10% polydispersity, a comparable radius of gyration ( ) and a major liposome particle mass of 118 kDa. The local bilayer structure of the liposome is found to have asymmetric electronic density profiles in the inner and outer leaflets, sandwiched by two PEGylated outer layers 5 nm thick. Cholesterol was found to effectively intervene in lipid chain packing, resulting in the thickening of the liposome bilayer, an increase in the area per lipid and an increase in liposome size, especially in the fluid phase of the liposome. These cholesterol effects show signs of saturation at cholesterol concentrations above 1:5 cholesterol:lipid molar ratio.
由于对高效药物载体的需求不断增加，脂质体的研发备受关注。此类脂质体的结构特征和热稳定性在药物运输和递送中至关重要。本文报道了通过小角和广角X射线散射以及与差示折光检测、多角度光散射（MALS）和动态光散射联用的不对称流场-流分级（AF4）系统对聚乙二醇化脂质体进行结构表征的结果。对由氢化大豆磷脂酰胆碱（HSPC）添加胆固醇形成的典型聚乙二醇化脂质体的综合分析表明，其平均流体动力学半径（ ）为52 nm，多分散性为10%，回转半径（ ）相当，主要脂质体颗粒质量为118 kDa。发现脂质体的局部双层结构在内层和外层小叶中具有不对称的电子密度分布，被两层5 nm厚的聚乙二醇化外层夹在中间。发现胆固醇有效地干预了脂质链堆积，导致脂质体双层增厚、每脂质面积增加和脂质体尺寸增大，尤其是在脂质体的流体相中。在胆固醇浓度高于1:5胆固醇:脂质摩尔比时，这些胆固醇效应显示出饱和迹象。
