Geusens B, Lambert J, De Smedt S C, Buyens K, Sanders N N, Van Gele M
Department of Dermatology, Ghent University Hospital, Belgium.
J Control Release. 2009 Feb 10;133(3):214-20. doi: 10.1016/j.jconrel.2008.10.003. Epub 2008 Oct 17.
The aim of this work was to develop a system that can deliver siRNA into cells present in the human epidermis. More specifically, we wanted to block the expression of a specific Myosin Va exon F containing isoform that is physiologically involved in melanosome transport in human melanocytes. Therefore, we prepared and investigated the capacity of ultradeformable cationic liposomes (UCLs) to deliver siRNA in hard-to-transfect human primary melanocytes. UCLs were formulated from different w:w ratios (6:1, 8:1 and 10:1) of the cationic lipid 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and the edge activator sodium cholate. Subsequently, UCL/siRNA complexes were prepared and their particle size, surface charge, deformability, cytotoxicity, transfection efficiency and long-term stability were tested. The best results were obtained with UCLs composed of a DOTAP/NaChol ratio of 6:1 (w:w) which are promising for future in vivo experiments.
这项工作的目的是开发一种能够将小干扰RNA（siRNA）递送至人表皮细胞的系统。更具体地说，我们想要阻断一种特定的含肌球蛋白Va外显子F的异构体的表达，该异构体在生理上参与人黑素细胞中黑素小体的转运。因此，我们制备并研究了超可变形阳离子脂质体（UCLs）在难以转染的人原代黑素细胞中递送siRNA的能力。UCLs由阳离子脂质1,2 - 二油酰基 - 3 - 三甲基铵丙烷（DOTAP）和边缘活化剂胆酸钠以不同的重量比（6:1、8:1和10:1）配制而成。随后，制备了UCL/siRNA复合物，并测试了它们的粒径、表面电荷、可变形性、细胞毒性、转染效率和长期稳定性。由DOTAP/NaChol比例为6:1（w:w）组成的UCLs取得了最佳结果，这对未来的体内实验很有前景。
