Supramolecular organization of S12363-liposomes prepared with two different remote loading processes
Supramolecular organization of S12363-liposomes prepared with two different remote loading processes
复制标题
DOI：
10.1016/j.bbamem.2008.11.017
复制
发表时间：
2009-05-01
影响因子：
3.4
通讯作者：
Ollivon, Michel
中科院分区：
文献类型：
--
作者：
Chemin, Caroline;Pean, Jean-Manuel;Ollivon, Michel
将S12363抗癌药物包封在脂质体中，以增加其治疗指数。基于酸性内脂质体隔室和碱性外相之间pH梯度或铵梯度的形成，使用两种不同的工艺实现S12363加载。鞘磷脂/胆固醇/胆固醇-PEG囊泡的两种方法均获得了高包封率（>90%）。荧光分光光度法测量表明，脂质体的特征在于两种加载过程的内部pH值均为4左右。该内部pH值在至少20天的时间内是稳定的。差示扫描量热法结合时间分辨同步辐射X射线衍射法研究了药物/载体的超分子结构。在硫酸铵中，S12363被插入到极性头基附近的双层中。在柠檬酸缓冲液中，S12363主要吸附在水-脂界面。药物分配到膜是不均匀的，并导致形成药物丰富和药物贫乏的领域。胆固醇的存在下，特别是在硫酸铵中，这种效果得到增强。总之，对于这两个过程，发现包封的药物在脂质体水性核心内，但与膜强烈相互作用。(C)2008 Elsevier B. V.保留所有权利。
The S12363 anticancer drug was encapsulated into liposomes in an attempt to increase its therapeutic index. Loading of S12363 was achieved using two different processes based on the formation of either a pH gradient or an ammonium gradient between the acidic inner liposomal compartment and the basic outer phase. High encapsulation yields (>90%) were obtained using both processes for sphingomyelin/cholesterol/cholesterol-PEG vesicles. Spectrofluorimetry measurements have shown that liposomes were characterized by an internal pH around 4 for both loading processes. This internal pH was stable over a period of at least 20 days. Differential scanning calorimetry coupled with time-resolved synchrotron X-ray diffraction was used to study the drug/carrier supramolecular organization. In ammonium sulfate, S12363 was inserted into the bilayer in the vicinity of the polar headgroup. In citrate buffer, S12363 was mainly adsorbed at the water-lipid interface. The drug partitioning into the membrane was inhomogeneous and led to the formation of drug-rich and drug-poor domains. This effect was enhanced in the presence of cholesterol, especially in ammonium sulfate. To conclude, for both processes, the encapsulated drug was found inside the liposome aqueous core but strongly interacting with the membrane. (C) 2008 Elsevier B.V. All rights reserved.