Synthesis of a single-tailed cationic lipid and investigation of its transfection

Single-tailed cationic lipids were originally reported to have low transfection efficiency and high toxicity in plasmid delivery. We hypothesized that particular single-tailed cationic lipids may also function in plasmid transfection. To test this hypothesis, we synthesized a new cationic lipid-oleo...

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Bibliographic Details
Published in:Journal of controlled release 1999-12, Vol.62 (3), p.345-358
Main Authors: Tang, Fuxing, Hughes, Jeffrey A
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cations - chemical synthesis
Cells, Cultured
Cetrimonium Compounds - chemistry
Cricetinae
DNA - pharmacokinetics
Drug Design
Female
Gene delivery
General pharmacology
Lipids - chemical synthesis
Liposome
Liposomes - genetics
Liposomes - pharmacokinetics
Medical sciences
Ornithine - chemistry
Ovary - physiology
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Plasmid DNA
Plasmids
Single-tailed
Time Factors
Transfection
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Summary:Single-tailed cationic lipids were originally reported to have low transfection efficiency and high toxicity in plasmid delivery. We hypothesized that particular single-tailed cationic lipids may also function in plasmid transfection. To test this hypothesis, we synthesized a new cationic lipid-oleoyl ornithinate (OLON). To decrease cytotoxicity, we then introduced a potential biodegradable ester bond in the tail of lipid yielding 6-lauroxyhexyl ornithinate (LHON). The data demonstrated that the cytotoxicity of LHON was lower than that of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or OLON. To investigate the transfection activity of the new lipids and determine the cellular uptake of DNA/liposome complexes, we compared the transfection of liposomes produced from double-tailed 1′,2′-dioleyl-sn-glycero-3′-succinyl-1, 6-hexanediol ornithine conjugate (DOGSHDO) with an ornithine headgroup, single-tailed OLON with an ornithine head group, double-tailed DOTAP with quaternary amine group, and single-tailed cetyltrimethylammonium bromide (CTAB) with a quaternary amine group. At the optimal ratios as defined in transfection experiments, OLON/DOPE had more than 10 times the transgene expression than other liposomes even though the DNA uptake was not necessarily greater. In the experiments comparing the release of DNA from DNA/liposome complexes by anionic substances, a greater fraction of DNA was released from DNA/OLON/DOPE complexes than that from DNA/DOTAP/DOPE complexes.
ISSN:0168-3659
1873-4995
DOI:10.1016/S0168-3659(99)00158-3