Effect of cationic lipid and matrix lipid composition on solid lipid nanoparticle-mediated gene transfer.
Effect of cationic lipid and matrix lipid composition on solid lipid nanoparticle-mediated gene transfer.
复制标题
DOI：
10.1016/j.ejpb.2003.10.015
复制
发表时间：
2004-03
期刊：
影响因子：
--
通讯作者：
Kerstin Tabatt;M. Sameti;C. Olbrich;R. Müller;C. Lehr
中科院分区：
文献类型：
--
作者：
Kerstin Tabatt;M. Sameti;C. Olbrich;R. Müller;C. Lehr
本研究旨在通过优化固体脂质纳米粒(SLN)的阳离子脂和基质脂组成来提高体外转染率。为此，使用两种不同的基质脂类和六种不同的阳离子洗涤剂来配制SLN。测试了这12种制剂的物理参数，如颗粒大小、Zeta电位和DNA结合能力，以及它们的生物学特性，如细胞毒性和体外转染率。SLN是通过热高压均质制备的，所有处方都是物理稳定的，并显示出高度的表面正电荷(+34~+45 mV)。对COS-1细胞的体外细胞毒性测试表明，细胞毒性强烈依赖于所使用的阳离子脂类。单尾型阳离子洗涤剂制备的SLN具有很强的细胞毒性。相比之下，双尾型阳离子脂类的耐受性都很好。阳离子脂蛋白和基质脂蛋白似乎同时决定了转染体的活性。在这里，十六烷基棕榈酸酯和N-[1-(2，3-二油酰氧基)丙基]-N，N，N-三甲基氯化铵的组合比所有其他测试组合的转染率要高得多。这些结果表明，只要选择好双尾阳离子脂类和基质脂类的良好组合，SLN就可以实现良好的耐受性和高效的体外转染性。
This investigation is focused on the enhancement of in vitro transfection activity by optimizing cationic lipid and matrix lipid composition of solid lipid nanoparticles (SLN). For this purpose SLN were formulated by using two different matrix lipids and six different cationic detergents. These 12 formulations were tested for physical parameters such as particle size, zeta potential and DNA-binding capacity, and also for their biological properties such as cytotoxicity and in vitro transfection efficiency. The SLN were produced by hot high-pressure homogenization, all formulations were physically stable and showed a highly positive surface charge (+34 to +45 mV). In vitro cytotoxicity measurements on COS-1 cells revealed that cytotoxicity is strongly dependent on the cationic lipid used. SLN made from one-tailed cationic detergents were highly cytotoxic. In contrast the two-tailed cationic lipids were all well tolerated. Transfection activity seems to be determined by both the cationic lipid and the matrix lipid used. Here, the combination of cetylpalmitate and N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride led to significantly higher transfection efficiencies than in all other tested combinations. These results indicate that well tolerated and highly efficient in vitro transfection could be achieved with SLN whenever selecting good combinations of two-tailed cationic lipids and matrix lipids.