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Novel cationic cholesterol derivative-based liposomes for serum-enhanced delivery of siRNA

Authors
Han, Su-EunKang, HyunguShim, Ga YongSuh, Min SungKim, Sun JaeKim, Jin-SeokOh, Yu-Kyoung
Issue Date
2-Apr-2008
Publisher
ELSEVIER SCIENCE BV
Keywords
cationic lipids; cholesterol derivatives; serum stability; siRNA delivery
Citation
INTERNATIONAL JOURNAL OF PHARMACEUTICS, v.353, no.1-2, pp.260 - 269
Journal Title
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume
353
Number
1-2
Start Page
260
End Page
269
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/14277
DOI
10.1016/j.ijpharm.2007.11.026
ISSN
0378-5173
Abstract
Most cationic liposomes used for gene delivery suffer from reduced transfection efficiency in the presence of serum. In this study, we report serum-enhanced delivery efficiency of siRNA via the use of newly synthesized liposomes that contain cationic lipids. Two cholesterol derivatives, cholesteryloxypropan-1-amine (COPA) and cholesteryl-2-an-noethylcarbamate (CAEC), were synthesized. A fluorescein label was then used to visualize cellular uptake of small interfering RNA (siRNA) via COPA or CAEC-based liposomes. The presence of serum had different effects on the cellular delivery of siRNA when siRNA was complexed to different cationic liposomes. CAEC-based liposomes showed significantly reduced cellular delivery of siRNA in serum-containing media as compared to serum-free media. Conversely, COPA-based liposomes (COPA-L) provided serum-enhanced delivery of siRNA in Hepal-6, A549, and Hela cell lines. Following delivery of the oncogene survivin-specific siRNA, COPA-L reduced the mRNA expression levels of the target gene more efficiently than did Lipofectamine 2000. The delivery of green fluorescent protein-specific siRNA with COPA-L reduced the expression of green fluorescent protein in 293T stable cell lines. The apoptosis of Hepal-6 significantly increased by delivery of survivin-specific siRNA by COPA-L. Additionally, Hepal-6, A549, and Hela cells were > 80% viable after treatment with COPA-L. These results suggest that the newly synthesized cholesterol derivative, COPA-L, could be further developed as a serum-enhanced delivery system of siRNA. (c) 2007 Elsevier B.V. All rights reserved.
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