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Enhanced gene expression in lung by a stabilized lipoplex using sodium chloride for complex formation
Author(s) -
Kawakami Shigeru,
Ito Yoshitaka,
Fumoto Shintaro,
Yamashita Fumiyoshi,
Hashida Mitsuru
Publication year - 2005
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.813
Subject(s) - sodium , chemistry , gene expression , chloride , lung , gene , microbiology and biotechnology , biophysics , medicine , pharmacology , biochemistry , biology , organic chemistry
Background In this study, we investigated the in vivo gene transfection efficacy of a ‘surface charge regulated’ (SCR) lipoplex, dispersed in the presence of an essential amount of NaCl during lipoplex formation. Methods SCR lipoplexes were prepared and their physicochemical properties were analyzed. After intravenous (i.v.) administration, transfection efficacy, distribution characteristics, and liver toxicity were evaluated in mice. Results At NaCl concentrations of 10 mM, the particle sizes of the SCR lipoplexes were about 120 nm and were compatible with a conventional lipoplex. However, fluorescent resonance energy transfer analysis revealed that cationic liposomes in the SCR lipoplexes increased fusion. After i.v. administration, the transfection activity in the lung of the SCR lipoplex (10 mM NaCl solution in the lipoplex) was approximately 10‐fold higher than that of the conventional lipoplex. Pharmacokinetic studies demonstrated a higher distribution in lung by the SCR lipoplex. When the gene expression levels of the SCR lipoplex and conventional lipoplex were compared, the SCR lipoplex at a dose of 30 µg was compatible with that of the conventional lipoplex at a dose of 50 µg. A significantly higher serum alanine aminotransferase (ALT) activity and TNFα concentration was observed by the conventional lipoplex (pDNA dose; 50 µg), but this was not the case for the SCR lipoplex (pDNA dose; 30 µg). Conclusions We demonstrated that the SCR lipoplex could enhance the transfection efficacy in the lung without increasing the liver toxicity. Hence, the information will be valuable for the future use, design, and development of lipoplexes for in vivo applications. Copyright © 2005 John Wiley & Sons, Ltd.