Hepatocyte-Selective Gene Transfer by Galactosylated Protein/Linear Polyethyleneimine/Plasmid DNA Complexes in Mice
Abstract:The purpose of this study was to improve gene delivery to the liver parenchymal cell (PC) following intravenous administration by reducing the aggregation of galactosylated carriers with erythrocytes, since the aggregation would restrict carrier to through the hepatic fenestra. We developed a new formulation using linear polyethyleneimine (PEI) with galactosylated bovine serum albumin (Gal-BSA) and plasmid DNA (pDNA) electrostatically (Gal-BSA/linear PEIcomplex). The particle size and zeta potential of the Gal-BSA/linear PEI complex were 71.6 ± 6.0 nm and 44.1 ± 0.50 mV and the complex did not aggregate with erythrocytes. The complex was more effectively taken up by HepG2 than NIH3T3 without the asialoglycoprotein receptor (ASGPR) expression, and its uptake was inhibited by the excess amount of galactose. After an intravenous injection of the Gal-BSA/linear PEI complex, high gene expression was observed in lung and the liver and it's liver gene expression was higher than that of an intraportally injected galactosylated PEI complexed with pDNA. Furthermore, high gene expression of the Gal-BSA/linear PEI complex was observed in hepatocyte compared with liver non-parenchymal cells. These results suggested the reduction of the aggregation with erythrocytes and PC selective gene expression by intravenous injection of the Gal-BSA/linear PEI in mice.
Document Type: Research Article
Publication date: 2007-09-01
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