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

被引:65
作者
Geusens, B. [1 ]
Lambert, J. [1 ]
De Smedt, S. C. [2 ]
Buyens, K. [2 ]
Sanders, N. N. [2 ,3 ]
Van Gele, M. [1 ]
机构
[1] Ghent Univ Hosp, Dept Dermatol, B-9000 Ghent, Belgium
[2] Univ Ghent, Lab Gen Biochem & Phys Pharm, B-9000 Ghent, Belgium
[3] Univ Ghent, Lab Gene Therapy, Dept Nutr Genet & Ethol, Fac Vet Med, B-9820 Merelbeke, Belgium
关键词
Ultradeformable liposomes; Delivery vehicle; Skin; Melanocytes; siRNA; DRUG CARRIERS; TRANSDERMAL DELIVERY; TRIAMCINOLONE-ACETONIDE; TRANSFECTION EFFICIENCY; TOPICAL APPLICATION; INTACT SKIN; DNA; VESICLES; EXPRESSION; IMMUNIZATION;
D O I
10.1016/j.jconrel.2008.10.003
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
引用
收藏
页码:214 / 220
页数:7
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