The Insertion Timing of PEGylated Lipids to Galactosylated Lipoplexes Is Important for Liver-Selective Transfection in Mice

Shintaro Fumoto; Naoki Taniguchi; Yuri Ikai; Naoki Yoshikawa; Hirotaka Miyamoto; Hitoshi Sasaki; Mitsuru Hashida; Shigeru Kawakami; Koyo Nishida

doi:doi:10.11648/j.ijgg.20160406.15

The Insertion Timing of PEGylated Lipids to Galactosylated Lipoplexes Is Important for Liver-Selective Transfection in Mice

Shintaro Fumoto, Naoki Taniguchi, Yuri Ikai, Naoki Yoshikawa, Hirotaka Miyamoto, Hitoshi Sasaki, Mitsuru Hashida, Shigeru Kawakami, Koyo Nishida

Published in International Journal of Genetics and Genomics (Volume 4, Issue 6)

Received: 10 March 2016 Accepted: 22 March 2016 Published: 22 March 2017

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Abstract

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.

Published in	International Journal of Genetics and Genomics (Volume 4, Issue 6)
DOI	10.11648/j.ijgg.20160406.15
Page(s)	68-78
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2017. Published by Science Publishing Group

Keywords

Gene Therapy, PEGylation, Galactosylated Liposomes, Targeting, Hepatocyte

References

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APA Style

Shintaro Fumoto, Naoki Taniguchi, Yuri Ikai, Naoki Yoshikawa, Hirotaka Miyamoto, et al. (2017). The Insertion Timing of PEGylated Lipids to Galactosylated Lipoplexes Is Important for Liver-Selective Transfection in Mice. International Journal of Genetics and Genomics, 4(6), 68-78. https://doi.org/10.11648/j.ijgg.20160406.15

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ACS Style

Shintaro Fumoto; Naoki Taniguchi; Yuri Ikai; Naoki Yoshikawa; Hirotaka Miyamoto, et al. The Insertion Timing of PEGylated Lipids to Galactosylated Lipoplexes Is Important for Liver-Selective Transfection in Mice. Int. J. Genet. Genomics 2017, 4(6), 68-78. doi: 10.11648/j.ijgg.20160406.15

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AMA Style

Shintaro Fumoto, Naoki Taniguchi, Yuri Ikai, Naoki Yoshikawa, Hirotaka Miyamoto, et al. The Insertion Timing of PEGylated Lipids to Galactosylated Lipoplexes Is Important for Liver-Selective Transfection in Mice. Int J Genet Genomics. 2017;4(6):68-78. doi: 10.11648/j.ijgg.20160406.15

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@article{10.11648/j.ijgg.20160406.15,
  author = {Shintaro Fumoto and Naoki Taniguchi and Yuri Ikai and Naoki Yoshikawa and Hirotaka Miyamoto and Hitoshi Sasaki and Mitsuru Hashida and Shigeru Kawakami and Koyo Nishida},
  title = {The Insertion Timing of PEGylated Lipids to Galactosylated Lipoplexes Is Important for Liver-Selective Transfection in Mice},
  journal = {International Journal of Genetics and Genomics},
  volume = {4},
  number = {6},
  pages = {68-78},
  doi = {10.11648/j.ijgg.20160406.15},
  url = {https://doi.org/10.11648/j.ijgg.20160406.15},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijgg.20160406.15},
  abstract = {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.},
 year = {2017}
}

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TY  - JOUR
T1  - The Insertion Timing of PEGylated Lipids to Galactosylated Lipoplexes Is Important for Liver-Selective Transfection in Mice
AU  - Shintaro Fumoto
AU  - Naoki Taniguchi
AU  - Yuri Ikai
AU  - Naoki Yoshikawa
AU  - Hirotaka Miyamoto
AU  - Hitoshi Sasaki
AU  - Mitsuru Hashida
AU  - Shigeru Kawakami
AU  - Koyo Nishida
Y1  - 2017/03/22
PY  - 2017
N1  - https://doi.org/10.11648/j.ijgg.20160406.15
DO  - 10.11648/j.ijgg.20160406.15
T2  - International Journal of Genetics and Genomics
JF  - International Journal of Genetics and Genomics
JO  - International Journal of Genetics and Genomics
SP  - 68
EP  - 78
PB  - Science Publishing Group
SN  - 2376-7359
UR  - https://doi.org/10.11648/j.ijgg.20160406.15
AB  - 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.
VL  - 4
IS  - 6
ER  -

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Author Information

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
Shigeru Kawakami

Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
Koyo Nishida

Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan

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APA Style

Shintaro Fumoto, Naoki Taniguchi, Yuri Ikai, Naoki Yoshikawa, Hirotaka Miyamoto, et al. (2017). The Insertion Timing of PEGylated Lipids to Galactosylated Lipoplexes Is Important for Liver-Selective Transfection in Mice. International Journal of Genetics and Genomics, 4(6), 68-78. https://doi.org/10.11648/j.ijgg.20160406.15

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ACS Style

Shintaro Fumoto; Naoki Taniguchi; Yuri Ikai; Naoki Yoshikawa; Hirotaka Miyamoto, et al. The Insertion Timing of PEGylated Lipids to Galactosylated Lipoplexes Is Important for Liver-Selective Transfection in Mice. Int. J. Genet. Genomics 2017, 4(6), 68-78. doi: 10.11648/j.ijgg.20160406.15

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AMA Style

Shintaro Fumoto, Naoki Taniguchi, Yuri Ikai, Naoki Yoshikawa, Hirotaka Miyamoto, et al. The Insertion Timing of PEGylated Lipids to Galactosylated Lipoplexes Is Important for Liver-Selective Transfection in Mice. Int J Genet Genomics. 2017;4(6):68-78. doi: 10.11648/j.ijgg.20160406.15

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@article{10.11648/j.ijgg.20160406.15,
  author = {Shintaro Fumoto and Naoki Taniguchi and Yuri Ikai and Naoki Yoshikawa and Hirotaka Miyamoto and Hitoshi Sasaki and Mitsuru Hashida and Shigeru Kawakami and Koyo Nishida},
  title = {The Insertion Timing of PEGylated Lipids to Galactosylated Lipoplexes Is Important for Liver-Selective Transfection in Mice},
  journal = {International Journal of Genetics and Genomics},
  volume = {4},
  number = {6},
  pages = {68-78},
  doi = {10.11648/j.ijgg.20160406.15},
  url = {https://doi.org/10.11648/j.ijgg.20160406.15},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijgg.20160406.15},
  abstract = {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.},
 year = {2017}
}

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TY  - JOUR
T1  - The Insertion Timing of PEGylated Lipids to Galactosylated Lipoplexes Is Important for Liver-Selective Transfection in Mice
AU  - Shintaro Fumoto
AU  - Naoki Taniguchi
AU  - Yuri Ikai
AU  - Naoki Yoshikawa
AU  - Hirotaka Miyamoto
AU  - Hitoshi Sasaki
AU  - Mitsuru Hashida
AU  - Shigeru Kawakami
AU  - Koyo Nishida
Y1  - 2017/03/22
PY  - 2017
N1  - https://doi.org/10.11648/j.ijgg.20160406.15
DO  - 10.11648/j.ijgg.20160406.15
T2  - International Journal of Genetics and Genomics
JF  - International Journal of Genetics and Genomics
JO  - International Journal of Genetics and Genomics
SP  - 68
EP  - 78
PB  - Science Publishing Group
SN  - 2376-7359
UR  - https://doi.org/10.11648/j.ijgg.20160406.15
AB  - 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.
VL  - 4
IS  - 6
ER  -

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