Ultradeformable cationic liposomes for delivery of small interfering RNA (siRNA) into human primary melanocytes

Ultradeformable cationic liposomes for delivery of small interfering RNA (siRNA) into human primary melanocytes
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DOI:
10.1016/j.jconrel.2008.10.003
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发表时间:
2009-02-10
影响因子:
10.8
通讯作者:
Van Gele, M.
Van Gele, M.
中科院分区:
医学1区
文献类型:
--
作者:
Geusens, B.;Lambert, J.;Van Gele, M.

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这项工作的目的是开发一种可以将siRNA递送到人表皮细胞中的系统。更具体地说,我们想阻断一种特定的肌球蛋白Va外显子F的表达,该外显子F含有在生理上参与人黑素细胞中黑素体转运的同种型。因此,我们制备并研究了超变形阳离子脂质体(UCL)在难以抑制的人原代黑素细胞中递送siRNA的能力。由不同w:w比(6:1、8:1和10:1)的阳离子脂质1,2-二油酰基-3-三甲基铵丙烷(DOTAP)和边缘活化剂胆酸钠配制UCL。随后,制备UCL/siRNA复合物,并测试其粒径、表面电荷、变形性、细胞毒性、转染效率和长期稳定性。使用由DOTAP/NaChol比率为6:1(w:w)组成的UCL获得了最佳结果,这对于未来的体内实验是有希望的。(C)2008 Elsevier B. V.保留所有权利。
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. (C) 2008 Elsevier B.V. All rights reserved.