title: Hepatic gene delivery system electrostatically assembled with glycyrrhizin.
abstract: In this study, a novel liver-targeted gene delivery vector was developed by electrostatically coating the cationic complex of pDNA and polyethylenimine (PEI) with glycyrrhizin (GL). The ternary complex, pDNA/PEI/GL, had approximately 100 nm stable particles with a negative charge surface. pDNA/PEI/GL showed high gene expression comparable to that of the complex of pDNA and PEI (pDNA/PEI) in human hepatoma cell line HepG2 without cytotoxicity and agglutination. After intravenous injection of pDNA/PEI/GL into mice, the highest gene expression was observed in the liver. pDNA/PEI/GL showed significantly higher gene expression in parenchymal cells than in nonparenchymal cells. On the basis of these results, we evaluated the pharmacological activity of the ternary complex including the pDNA encoding insulin (pCMV-Ins). The pCMV-Ins/PEI/GL decreased blood glucose concentrations 24 h after its intravenous administration to mice. The ternary complex of pDNA, PEI, and GL may be a promising liver-targeted gene vector.
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital , 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kurosaki
authors.forename: Saki
authors.initials: S
authors.lastname: Kawanabe
authors.forename: Yukinobu
authors.initials: Y
authors.lastname: Kodama
authors.forename: Shintaro
authors.initials: S
authors.lastname: Fumoto
authors.forename: Koyo
authors.initials: K
authors.lastname: Nishida
authors.forename: Hiroo
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Norihide
authors.initials: N
authors.lastname: Higuchi
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Takashi
authors.initials: T
authors.lastname: Kitahara
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D004337:Drug Carriers / Q000009:adverse effects / Q000737:chemistry; D018014:Gene Transfer Techniques / Q000009:adverse effects; D005822:Genetic Vectors / Q000009:adverse effects / Q000737:chemistry; D019695:Glycyrrhizic Acid / Q000008:administration & dosage* / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D008297:Male; D058503:Mesophyll Cells / Q000378:metabolism; D051379:Mice; D011094:Polyethyleneimine / Q000737:chemistry; D055672:Static Electricity
chemical_list: D004337:Drug Carriers; D019695:Glycyrrhizic Acid; D011094:Polyethyleneimine