Liver-targeted siRNA delivery by polyethylenimine (PEI)-pullulan carrier.
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.
Kang
Jeong-Hun
JH
Department of Biomedical Engineering, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan.
Tachibana
Yoichi
Y
Kamata
Wakako
W
Mahara
Atsushi
A
Harada-Shiba
Mariko
M
Yamaoka
Tetsuji
T
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
D004337:Drug Carriers; D005936:Glucans; D034741:RNA, Small Interfering; C009109:pullulan; D011094:Polyethyleneimine; D019793:Fluorescein