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

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

1 ( 1 )  , pp.1 - 11 , 2016-04-14 , Science Publishing Group
Description
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.
Full-Text

http://naosite.lb.nagasaki-u.ac.jp/dspace/bitstream/10069/36354/1/GCT1_1.pdf

Number of accesses :  

Other information