Taxonomic group: fungi / Ascomycota
(Phylum: Ascomycota)
NCBI PubMed ID: 22974833Publication DOI: 10.1016/j.jconrel.2012.08.030Journal NLM ID: 8607908Publisher: Amsterdam: Elsevier Science Publishers
Correspondence: yamtet
ri.ncvc.go.jp
Institutions: Department of Biomedical Engineering, Advanced Medical Engineering Center, National Cerebral and Cardiovascular Center Research Institutes, Osaka, Japan, Division of Bioorganic Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan, Department of Molecular Innovation in Lipidology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan
Apolipoprotein B (Apo B) is a key amphipathic glycoprotein compound in the metabolism of plasma lipoproteins (mainly very low-density lipoprotein (VLDL) and LDL). Inhibition of Apo B synthesis by short interfering RNA (siRNA) targeting Apo B (Apo B siRNA) is very efficient for serum LDL reduction. In the present study, the chemically modified Apo B siRNA (Apo B-siBNA) with the increased enzymatic stability was selected. We developed a cationic conjugate for efficient delivery of Apo B-siBNA into the liver by introducing pullulan with different molecular weights (MWs) (5900 and 107,000) into polyethylenimine (PEI). Introduction of pullulan into PEI dramatically decreased mortality and lung damage after systemic injection of the conjugate/Apo B-siBNA complexes into mice. The PEI-pullulan carrier prepared with high MW pullulan (107,000) was more stable in the blood stream and showed higher fluorescence levels in the liver for a longer time than the carrier prepared with low MW pullulan (5900). Moreover, efficient reduction of serum LDL and Apo B mRNA in the liver was observed in mice injected with PEI-pullulan (MW, 107,000)/Apo B-siBNA, whereas there was no or little change in serum LDL and Apo B mRNA in livers of mice treated with Apo B-siBNA alone, PEI/Apo B-siBNA, and PEI-pullulan (MW, 5900)/Apo B-siBNA. These results suggest that combining a liver-targeted gene delivery system with chemically modified Apo B siRNA efficiently reduces the level of serum LDL and Apo B mRNA in the liver.
pullulan, cholesterol, Apo B, liver-targeted delivery
Structure type: polymer chemical repeating unit ; 5900-107000
Location inside paper: p.120, column 1, paragraph 2
Trivial name: pullulan
Compound class: O-polysaccharide, glucan
Contained glycoepitopes: IEDB_140629,IEDB_142488,IEDB_144998,IEDB_146664,IEDB_420419,IEDB_420420,IEDB_420421,IEDB_857742,IEDB_983931,SB_192
Methods: biological assays, electrophoresis, zeta potential measurement, fluorescence binding assay, derivatization, acid–base titration
Biological activity: polyethylenimine-pullulan complex is effective carrier for liver-targeted gene delivery
Related record ID(s): 45035, 45814, 45934, 45961, 46041, 47851, 48389, 48424, 48425, 48441, 48447, 48467, 48468, 48469, 49231, 49289, 49953, 49977, 49978, 49979, 49995, 49999, 50000, 50002, 50007, 50014, 50071, 50081, 50082, 50083, 50111, 50113, 104020
NCBI Taxonomy refs (TaxIDs): 5580Reference(s) to other database(s): GTC:G71532WE
Show glycosyltransferases
There is only one chemically distinct structure:
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