title: Liver-targeted siRNA delivery by polyethylenimine (PEI)-pullulan carrier.
abstract: Recently, small interfering RNA (siRNA)-based therapeutics have been used to treat diseases. Efficient and stable siRNA delivery into disease cells is important in the use of this agent for treatment. In the present study, pullulan was introduced into polyethylenimine (PEI) for liver targeting. PEI/siRNA or pullulan-containing PEI/siRNA complexes were delivered into mice through the tail vein either by a hydrodynamics- or non-hydrodynamics-based injection. The incidence of mortality was found to increase with an increase in the nitrogen/phosphorus (N/P) ratio of PEI/siRNA complexes. Moreover, the hydrodynamics-based injection increased mice mortality. Introduction of pullulan into PEI dramatically reduced mouse death after systemic injection. After systemic injection, the PEI/fluorescein-labeled siRNA complex increased the level of fluorescence in the lung and the PEI-pullulan/siRNA complex led to an increased fluorescence level in the liver. These results suggest that the PEI-pullulan polymer may be a useful, low toxic means for efficient delivery of siRNA into the liver.
authors.affiliation: Department of Biomedical Engineering, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan.
authors.forename: Jeong-Hun
authors.initials: JH
authors.lastname: Kang
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Tachibana
authors.forename: Wakako
authors.initials: W
authors.lastname: Kamata
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mahara
authors.forename: Mariko
authors.initials: M
authors.lastname: Harada-Shiba
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Yamaoka
mesh_terms: D000818:Animals; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D019793:Fluorescein; D005936:Glucans / Q000627:therapeutic use; D007267:Injections; D008099:Liver; D051379:Mice; D011094:Polyethyleneimine / Q000627:therapeutic use; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D015996:Survival Rate
chemical_list: D004337:Drug Carriers; D005936:Glucans; D034741:RNA, Small Interfering; C009109:pullulan; D011094:Polyethyleneimine; D019793:Fluorescein