Synergistic effect of poly(ethylenimine) on the transfection efficiency of galactosylated chitosan/DNA complexes

• Published in: Journal of controlled release Vol. 105; no. 3; pp. 354 - 366
• Main Authors: Kim, Tae Hee, Kim, Su Il, Akaike, Toshihiro, Cho, Chong Su
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 20-07-2005; Elsevier
• Subjects: Biological and medical sciences; Cell Line, Tumor; Cell Survival - drug effects; Chitosan - pharmacology; Disaccharides; DNA - administration & dosage; DNA - chemistry; DNA - genetics; Drug Synergism; Electrophoresis, Agar Gel; Enzyme Inhibitors - pharmacology; Flow Cytometry; Galactose - pharmacology; Galactosylated chitosan/DNA complexes; General pharmacology; Genes, Reporter - genetics; Hepatocyte-targeting gene delivery; Humans; Liver - metabolism; Luciferases - genetics; Macrolides - pharmacology; Medical sciences; Microscopy, Confocal; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Poly(ethylenimine); Polyethyleneimine - pharmacology; Synergistic effect; Transfection; Transfection efficiency; Poly(ethylenimine); Synergistic effect; Hepatocyte-targeting gene delivery; Transfection efficiency; Galactosylated chitosan/DNA complexes; Target; Pharmaceutical technology; Transfection; Targeting; Hepatocyte; Galaetosylaled chitosan/DNA complexes; Poly(ethylenimine); Transfection efficiency; Synergistic effect; DNA; Chitosan; Gene therapy; In vitro; Genetic transfer
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2005.03.024

The use of chitosan for gene delivery is limited due to the low transfection efficiency and difficulty in transfecting into a variety of cell types, especially the hepatoma cells. In order to solve this problem, lactobionic acid (LA) bearing galactose group was coupled with water-soluble chitosan (WSC) for liver specificity and poly(ethylenimine) (PEI) was combined to galactosylated chitosan (GC)/DNA complexes to enhance the transfection efficiency. For initial study, the effect of PEI on the transfection efficiency of WSC/DNA complex was studied in HeLa, A549 and 293 T cells, and bafilomycin A1 was used to ascertain the mechanism of synergistic effect. Transfection efficiency, cytotoxicity, and physicochemical properties of GC/DNA complex combined with PEI were investigated to determine the potential for the hepatocyte-targeting. The combination of PEI with WSC/DNA and GC/DNA complex dramatically increased the luciferase expression 10- to 1000-fold in various cell lines, and the synergistic effect was proved to be induced by proton sponge effect of PEI. The transfection of GC/DNA complex in HepG2 was much higher than that of WSC/DNA even after combination with PEI, and was highly inhibited in the presence of galactose. Cytotoxicity of PEI was much decreased by combination with GC/DNA complex. And PEI was proved to be coated on the surface of GC/DNA complex through the ionic interaction.