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

Seok Min Kwon, Hae Yun Nam, Taehwan Nam, Kyeongsoon Park, Seulki Lee, Kwangmeyung Kim, Ick Chan Kwon, Jun Kim, Dongmin Kang, Jae Hyung Park, Seo Young Jeong

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39 Scopus citations

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 1 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.

Original languageEnglish
Pages (from-to)89-97
Number of pages9
JournalJournal of Controlled Release
Volume128
Issue number1
DOIs
StatePublished - 22 May 2008

Bibliographical note

Funding Information:
This work was supported by a grant from the Ministry of Science and Technology under the Real-Time Molecular Imaging Project, by the Global Research Project, and by Seoul R&BD Program in Korea.

Keywords

  • Bioluminescent imaging
  • Cationic lipid-based emulsions
  • In vivo gene expression
  • In vivo toxicity
  • Non-viral gene carrier

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