Enhancement of polyethylene glycol (PEG)-modified cationic liposome-mediated gene deliveries: effects on serum stability and transfection efficiency

Enhancement of polyethylene glycol (PEG)-modified cationic liposome-mediated gene deliveries: effects on serum stability and transfection efficiency
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DOI:
10.1211/002235702928
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发表时间:
2003-04-01
影响因子:
3.3
通讯作者:
Kim, CK
Kim, CK
中科院分区:
医学3区
文献类型:
--
作者:
Kim, JK;Choi, SH;Kim, CK

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本研究采用聚乙二醇(PEG)接枝法和添加PEG法对阳离子脂质体进行修饰,并比较了转染复合物的物理性质和体外转染效率以及延长体内循环的效果。将质粒DNA与阳离子脂质体(由DSPE-PEG 2000和阳离子脂质体组成)混合,制备PEG接枝转染复合物。通过向阳离子脂质体和质粒DNA的混合物中加入DSPE-PEG 2000来制备加入PEG的转染复合物。与常规转染复合物相比,PEG修饰的转染复合物的粒径(类似于200 nm)在4周内略有变化。在血清存在下,常规转染复合物的转染效率降低,而PEG修饰的转染复合物的转染效率得以保持。此外,常规转染复合物的转染效率在储存时显著降低。然而,PEG修饰的转染复合物的转染效率是稳定的,即使在储存两周后。在体外转染效率中,PEG接枝和PEG添加的转染复合物之间没有差异。当通过尾静脉将常规的、PEG接枝的和PEG添加的转染复合物施用到小鼠中时,与其他转染复合物相比,PEG添加的转染复合物显示出质粒DNA的延长的循环。这些结果表明,PEG添加的转染复合物可能是一个有用的非病毒载体,因为它们的制备简单,增强的稳定性和延长的循环相比,传统的转染复合物。
In this study, we modified cationic liposomes either by polyethylene glycol (PEG)-grafting or PEG-adding methods, and compared the physical properties of transfection complexes and transfection efficiency in-vitro and prolonged circulation in-vivo. The PEG-grafted transfection complexes were prepared by mixing plasmid DNA with PEG-grafted cationic liposomes, which were composed of DSPE-PEG 2000 and cationic lipids. The PEG-added transfection complexes were prepared by adding DSPE-PEG 2000 to the mixture of cationic liposomes and plasmid DNA. The particle sizes of the PEG-modified transfection complexes (similar to200nm) changed a little over 4 weeks compared with the conventional transfection complexes. In the presence of serum, the transfection efficiency of the conventional transfection complexes was lowered whereas the transfection efficiency of the PEG-modified transfection complexes was maintained. Moreover, the transfection efficiency of the conventional transfection complexes was significantly reduced when they were stored. However, the transfection efficiency was stable for the PEG-modified transfection complexes, even after two weeks of storage. Of the in-vitro transfection efficiencies, there was no difference between PEG-grafted and PEG-added transfection complexes. When the conventional, PEG-grafted, and PEG-added transfection complexes were administered into mice by the tail vein, the PEG-added transfection complexes showed a prolonged circulation of plasmid DNA compared with other transfection complexes. These results suggest that the PEG-added transfection complexes could be a useful non-viral vector because of their simplicity in preparation, enhanced stability and prolonged circulation compared with the conventional transfection complexes.