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, Kwang Meyung Kim, Ick Chan Kwon, Jun Kim, Dongmin Kang, Jae Hyung Park, Seo Young Jeong

Research output: Contribution to journalArticle

35 Citations (Scopus)

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
Publication statusPublished - 2008 May 22
Externally publishedYes

Fingerprint

Emulsions
Lipids
Gene Expression
DNA
Genes
Propane
Oils
Plasmids
Squalene
Poisons
Reporter Genes
Liposomes
Intravenous Injections
Genetic Therapy
Transfection
Spleen

Keywords

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

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

In vivo time-dependent gene expression of cationic lipid-based emulsion as a stable and biocompatible non-viral gene carrier. / Kwon, Seok Min; Nam, Hae Yun; Nam, Taehwan; Park, Kyeongsoon; Lee, Seulki; Kim, Kwang Meyung; Kwon, Ick Chan; Kim, Jun; Kang, Dongmin; Park, Jae Hyung; Jeong, Seo Young.

In: Journal of Controlled Release, Vol. 128, No. 1, 22.05.2008, p. 89-97.

Research output: Contribution to journalArticle

Kwon, Seok Min ; Nam, Hae Yun ; Nam, Taehwan ; Park, Kyeongsoon ; Lee, Seulki ; Kim, Kwang Meyung ; Kwon, Ick Chan ; Kim, Jun ; Kang, Dongmin ; Park, Jae Hyung ; Jeong, Seo Young. / In vivo time-dependent gene expression of cationic lipid-based emulsion as a stable and biocompatible non-viral gene carrier. In: Journal of Controlled Release. 2008 ; Vol. 128, No. 1. pp. 89-97.
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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.",
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AU - Nam, Hae Yun

AU - Nam, Taehwan

AU - Park, Kyeongsoon

AU - Lee, Seulki

AU - Kim, Kwang Meyung

AU - Kwon, Ick Chan

AU - Kim, Jun

AU - Kang, Dongmin

AU - Park, Jae Hyung

AU - Jeong, Seo Young

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N2 - 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.

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