title: Intracellular trafficking is the important process that determines the optimal charge ratio on transfection by galactosylated lipoplex in HEPG2 cells.
abstract: The purpose of the present study was to gain insight into the major factors affecting transfection efficiency with galactosylated lipoplex in HepG2 cells. In this study, lipoplex and galactosylated lipoplex were examined at different charge ratios (- : +): 1.0 : 1.2, 1.0 : 2.3, 1.0 : 3.1, 1.0 : 4.7, and 1.0 : 7.0. The particle size and zeta potential of the both lipoplexes was dependent on the charge ratio. Cellular uptake was evaluated by using [(32)P]-labeled pCMV-Luc and this showed that the cellular uptake of galactosylated lipoplex was significantly higher than that of lipoplex at a charge ratio ranging from 1.0 : 2.3 to 1.0 : 7.0. As the charge ratio increased in both lipoplexes, the apparent cellular uptake increased. Transfection activity by galactosylated lipoplex was significantly higher than that by lipoplex except at a charge ratio of 1.0 : 7.0. The optimal charge ratio for transfection efficacy was 1.0 : 2.3 and transfection was reduced at higher charge ratios. Both lipoplexes exhibited no significant cytotoxicity at any charge ratio. In conclusion, it is suggested that intracellular trafficking, rather than the degree of uptake and cytotoxicity, is the important process that determines the optimal charge ratio of galactosylated lipoplex in HepG2 cells.
authors.affiliation: Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Saito
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kawakami
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Yabe
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Yamashita
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Hashida
mesh_terms: D001692:Biological Transport; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005697:Galactosides / Q000493:pharmacokinetics*; D006801:Humans; D008081:Liposomes; D008099:Liver / Q000378:metabolism; D010316:Particle Size; D014162:Transfection / Q000379:methods*
chemical_list: D005697:Galactosides; D008081:Liposomes