Pulmonary gene delivery of hybrid vector, lipopolyplex containing N-lauroylsarcosine, via the systemic route
Pulmonary gene delivery of hybrid vector, lipopolyplex containing N-lauroylsarcosine, via the systemic route
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DOI：
10.1016/j.jconrel.2009.02.005
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发表时间：
2009-06-19
影响因子：
10.8
通讯作者：
Sasaki, Hitoshi
中科院分区：
文献类型：
--
作者：
Kurosaki, Tomoaki;Kishikawa, Reiko;Sasaki, Hitoshi
我们新制备了含有n -月桂酰肌氨酸（LS）的脂质复合物作为肺基因通过全身途径传递的杂交载体。脂质体由聚乙烯亚胺（PEI）、N-[1-（2,3-二聚氧基）丙基]-N，N，N-三甲基氯化铵（DOTMA）、LS和质粒DNA （pDNA）组成。LS的加入对PEI、DOTMA和pDNA脂质复合物（2P-2D脂质复合物）的粒径变化不大，但IS的加入降低了高zeta电位。含有低zeta电位LS的脂质复合物与红细胞聚集较少，细胞毒性较低。在HepG2细胞中，含有LS的脂质复合物表现出与脂质复合物2P-2D相当的高转基因效率。经小鼠静脉注射后，含有LS的脂复合物显示出较高的转基因效率，与脂复合物2P-2D相当。特别是含有LS的脂质复合物在肺中表现出极高的转基因效率。通过对最佳配方的分析，我们发现LS对肺内高转基因效率的贡献指数为76.7%。这些结果表明含有LS的脂质复合物是一种安全、有用的具有肺指向性的基因传递载体。(C) 2009 Elsevier B.V.版权所有
We newly prepared lipopolyplexes containing N-lauroylsarcosine (LS) as a hybrid vector for pulmonary gene delivery via the systemic route. Lipopolyplexes were composed of polyethylenimine (PEI), N-[1-(2,3-dioleyloxy) propyl]-N,N,N-trimethlylammonium chloride (DOTMA), LS, and plasmid DNA (pDNA). The particle size of lipopolyplex of PEI, DOTMA, and pDNA (lipopolyplex 2P-2D) was not largely changed by the addition of LS, although the addition of IS decreased the high zeta potential. Lipopolyplexes containing LS with low zeta potential showed little aggregation with erythrocytes and low cytotoxicity. In HepG2 cells, lipopolyplexes containing LS showed high transgene efficiency comparable to lipopolyplex 2P-2D. After intravenous injection of the complexes into mice, lipopolyplexes containing LS showed high transgene efficiency, comparable to lipopolyplex 2P-2D. In particular, lipopolyplexes containing LS showed extremely high transgene efficiency in the lung. As a result of the analysis to identify optimum formulations, we discovered that LS contributed to the high transgene efficiency in the lung as 76.7% of the contribution index. These results suggest that lipopolyplexes containing LS are safe and useful gene delivery vectors with lung directivity. (C) 2009 Elsevier B.V. All rights reserved.