Partial hepatectomy enhances polyethylenimine-mediated plasmid DNA delivery.
Polyethylenimine (PEI) is widely used for non-viral transfection in vitro and in vivo. Hepatectomy is an interesting and considerable factor modifying PEI-mediated gene expression. We investigated the gene expression in mice over time following partial hepatectomy after an intravenous injection of PEI/plasmid DNA (pDNA) complex. pDNA encoding firefly luciferase was used as the model reporter gene. The hepatectomized liver was rapidly regenerated until 72 h. After 168 h, the liver weight of hepatectomized mice was similar to that of control mice. Slight liver function impairment was only observed at 1-24 h after hepatectomy in alanine aminotransferase and aspartate aminotransferase levels. Luciferase activity in the liver of partial hepatectomized mice at 48 h after partial hepatectomy increased by 70 times compared with that of control mice; however, luciferase activities did not significantly differ between hepatectomized mice and control mice in the spleen, lung, kidney, and heart. Among the lobes, luciferase activity by gram of tissue was not significantly different, indicating that gene expression enhancement by partial hepatectomy occurred equally throughout the liver. In conclusion, our findings demonstrate that liver resection is an influencing factor on PEI-mediated gene delivery in mice. These results indicate the necessity of considering cell division in PEI-mediated pDNA delivery.
Tada
Yuki
Y
Department of Hospital Pharmacy, Nagasaki University Hospital of Medicine and Dentistry, Nagasaki, Japan.
Kitahara
Takashi
T
Yoshioka
Takashi
T
Nakamura
Tadahiro
T
Ichikawa
Nobuhiro
N
Nakashima
Mikiro
M
Nishida
Koyo
K
Nakamura
Junzo
J
Sasaki
Hitoshi
H
D000818:Animals; D004247:DNA / Q000008:administration & dosage*; D015870:Gene Expression; D006498:Hepatectomy; D008115:Liver Regeneration; D051379:Mice; D010957:Plasmids; D011094:Polyethyleneimine / Q000737:chemistry*
D011094:Polyethyleneimine; D004247:DNA