In vivo time-dependent gene expression of cationic lipid-based emulsion as a stable and biocompatible non-viral gene carrier

Authors
Kwon, Seok MinNam, Hae YunNam, TaehwanPark, KyeongsoonLee, SeulkiKim, KwangmeyungKwon, Ick ChanKim, JunKang, DongminPark, Jae HyungJeong, Seo Young
Issue Date
2008-05-22
Publisher
ELSEVIER SCIENCE BV
Citation
JOURNAL OF CONTROLLED RELEASE, v.128, no.1, pp.89 - 97
Abstract
To make stable and biocompatible non-viral gene carriers for therapeutic gene therapy, we developed a cationic lipid-based emulsion (CLE) prepared by an oil-in-water (O/W) emulsion method, wherein squalene oil was used as an oil core and the cationic lipid, 1,2-dioleoyl-sn-glycero-3-trimethylammonium-propane (DOTAP), was employed as an emulsifier. To evaluate in vivo characteristics such as toxicity and time-dependent gene expression, a bioluminescence reporter gene in pCMV-luc plasmid DNA was simply mixed with CLE in aqueous condition, resulting in a CLE/DNA complex. The CLE/DNA complex was optimized to form a compact and stable nano-sized particle by adding different amounts of plasmid DNA, and an optimal cationic lipid-to-DNA (C/D) weight ratio of 4 was identified. Freshly prepared CLE/DNA complex, with a C/D of 4, showed a high transfection efficiency and minimal cytotoxicity in vitro, compared to controls of a liposome (DOTAP)/DNA complex and a branched poly(ethyleneimine) (Mw=25 kDa) (bPEI)/DNA complex, respectively. The in vivo characteristics of the CLE/DNA complex were evaluated after intravenous injection into Balb/c mice. Time-dependent gene expression data in vivo were obtained using a non-invasive, whole animal bioluminescence imaging system. These data showed that the CLE/DNA complex offered prolonged high-level gene expression for I week, particularly in the liver and spleen. On the other hand, the controls of DOTAP/DNA complex and bPEI/DNA complex showed a relatively lower gene expression, because of the unstable and toxic properties of the control carriers. Our in vivo gene expression data demonstrate the potential of the CLE/DNA complex as a non-viral gene carrier for in vivo gene delivery. (C) 2008 Elsevier B.V. All rights reserved.
Keywords
NONIONIC SURFACTANTS; PLASMID DNA; DELIVERY; LIPOSOMES; THERAPY; TRANSFECTION; COMPLEXES; CELLS; VITRO; STABILITY; NONIONIC SURFACTANTS; PLASMID DNA; DELIVERY; LIPOSOMES; THERAPY; TRANSFECTION; COMPLEXES; CELLS; VITRO; STABILITY; cationic lipid-based emulsions; non-viral gene carrier; in vivo toxicity; in vivo gene expression; bioluminescent imaging
ISSN
0168-3659
URI
https://pubs.kist.re.kr/handle/201004/133483
DOI
10.1016/j.jconrel.2008.02.004
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KIST Article > 2008
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