Law Sai-Lung, Chuang Tzu-Chao, Kao Ming-Ching, Lin Yen-Shing, Huang Kuo-Jung
Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan 11217, ROC.
Drug Deliv. 2006 Jan-Feb;13(1):61-7. doi: 10.1080/10717540500309024.
A cationic liposome system consisting of sphingosine (SP) and dioleoylphosphatidylethanolamine (DOPE) was developed for in vitro and in vivo gene transfer. A nonionic surface active agent of poloxamer 188 was incorporated in the formulations to stabilize the DNA/liposome complex. Comparison of the results obtained from systems with and without the effect of poloxamer 188 was made to investigate the efficiency of gene expression. In vitro transfection study of the DNA/liposome complex showed that with the effect of poloxamer 188, gene transfer into some cell lines was enhanced. In vivo systemic delivery of the DNA/liposome complex with poloxamer 188 demonstrated gene expression with improved luciferase activity in all major organs including lung, spleen, heart, liver, and kidney. High level transgene activity was found in lung and spleen with prolonged gene expression. This was attributed to poloxamer 188 that stabilized the liposome system and produced homogeneous DNA/liposome complex for enhancement of gene delivery.
开发了一种由鞘氨醇(SP)和二油酰磷脂酰乙醇胺(DOPE)组成的阳离子脂质体系统,用于体外和体内基因转移。在制剂中加入泊洛沙姆188这种非离子表面活性剂,以稳定DNA/脂质体复合物。对有和没有泊洛沙姆188作用的系统所得结果进行比较,以研究基因表达效率。DNA/脂质体复合物的体外转染研究表明,在泊洛沙姆188的作用下,向某些细胞系的基因转移得到增强。在体内将含有泊洛沙姆188的DNA/脂质体复合物进行全身给药,结果显示在包括肺、脾、心脏、肝脏和肾脏在内的所有主要器官中,荧光素酶活性提高,出现了基因表达。在肺和脾中发现了高水平的转基因活性,且基因表达持续时间延长。这归因于泊洛沙姆188稳定了脂质体系统,并产生了均匀的DNA/脂质体复合物,从而增强了基因传递。