Abstract:
:We studied the intrahepatic disposition characteristics of galactosylated polyethylenimine (Gal-PEI)/plasmid DNA (pDNA) complexes using rat liver perfusion experiment. After intraportal administration, transfection activity in liver of Gal-PEI complexes was approximately 26-fold higher than that of native PEI complexes. To evaluate the relationship between hepatic gene expression and disposition profiles, hepatic disposition of Gal-PEI complexes were pharmacokinetically analyzed by use of perfused rat liver, which enables uptake characteristics intrinsic to the liver to be elucidated. Moment analysis revealed that both complexes exhibited very high single-pass extraction. To characterize each kinetic process in hepatic uptake of Gal-PEI complexes, their outflow profiles were analyzed based on a two-compartment dispersion model. Consequently, the tissue binding affinity of Gal-PEI complexes was 3.0-fold larger than that of native PEI complexes, suggesting the increasing of hepatic binding affinity much enhanced the hepatic gene transfection efficiency. In contrast, galactosylation of PEI did not affected internalization (and/or sequestration) rate.
journal_name
Drug Metab Pharmacokinetjournal_title
Drug metabolism and pharmacokineticsauthors
Fumoto S,Kawakami S,Ishizuka M,Nishikawa M,Yamashita F,Hashida Mdoi
10.2133/dmpk.18.230subject
Has Abstractpub_date
2003-01-01 00:00:00pages
230-7issue
4eissn
1347-4367issn
1880-0920pii
JST.JSTAGE/dmpk/18.230journal_volume
18pub_type
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