The Insertion Timing of PEGylated Lipids to Galactosylated Lipoplexes Is Important for Liver-Selective Transfection in Mice
International Journal of Genetics and Genomics
Volume 4, Issue 6, December 2016, Pages: 68-78
Received: Mar. 10, 2016;
Accepted: Mar. 22, 2016;
Published: Mar. 22, 2017
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Shintaro Fumoto, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
Naoki Taniguchi, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
Yuri Ikai, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
Naoki Yoshikawa, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
Hirotaka Miyamoto, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
Hitoshi Sasaki, Department of Hospital Pharmacy, Nagasaki University Hospital, Nagasaki, Japan
Mitsuru Hashida, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan; Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto, Japan
Shigeru Kawakami, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
Koyo Nishida, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
In the present study, we demonstrated the importance of PEGylation timing of galactosylated liposome/plasmid DNA (pDNA) complexes (lipoplexes) for liver-selective transfection in mice. Because a fenestrated endothelium can be a barrier for penetration of lipoplexes though sinusoids, the particle size of lipoplexes is one of the determining factors for in vivo liver parenchymal cell (hepatocyte, PC)-selective transfection. Here, we found that syn-insertion, as a novel PEGylation timing, was useful to control the particle size of galactosylated lipoplexes. Syn-insertion of PEGylated lipids was performed by simple mixing of pDNA solution containing PEGylated lipids and dispersion of the cationic liposomes. Both syn- and pre-insertion of PEGylated lipids decreased the particle size of lipoplexes, whereas post-insertion did not. Moreover, syn-insertion of PEGylated lipids to galactosylated lipoplexes improved liver selectivity and the PC/non-parenchymal cell ratio of transgene expression after intravenous injection in mice. Hence, these data will be valuable for the design and preparation of PEGylated lipoplexes for gene targeting.
The Insertion Timing of PEGylated Lipids to Galactosylated Lipoplexes Is Important for Liver-Selective Transfection in Mice, International Journal of Genetics and Genomics.
Vol. 4, No. 6,
2016, pp. 68-78.
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