ArticlePharmaceutical research2003
Analysis of hepatic disposition of galactosylated cationic liposome/plasmid DNA complexes in perfused rat liver.
Article in Pharmaceutical research, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Poly-L-Lysine-Lactobionic Acid-Capped Selenium Nanoparticles for Liver-Targeted Gene Delivery.International journal of molecular sciences · 2022Article
- Understanding In Vivo Fate of Nucleic Acid and Gene Medicines for the Rational Design of Drugs.Pharmaceutics · 2021Review
- Article
- Retracted: Inhibition of hepatitis C virus replication by intracellular delivery of multiple siRNAs by nanosomes.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
- Stability of lyophilized siRNA nanosome formulations.International journal of pharmaceutics · 2012Article
- Development and optimization of nanosomal formulations for siRNA delivery to the liver.European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V · 2012Article
- Novel pentablock copolymers for selective gene delivery to cancer cells.Pharmaceutical research · 2009Article
Corrections and comments
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Authors and funding
6 authors.
Funding
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Abstract
purposeTo determine the intrahepatic disposition characteristics of galactosylated liposome/plasmid DNA (pDNA) complexes in perfused rat liver.
methodsGalactosylated liposomes containing N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA), cholesterol (Chol), and cholesten-5-yloxy-N-14-[(1-imino-2-D-thiogalactosylethyl)amino]butyl] formamide (Gal-C4-Chol) were prepared. The liposome/[32P]-labeled pDNA complexes were administered to perfused liver, and the venous outflow patterns were analyzed based on a two-compartment dispersion model.
resultsThe single-pass hepatic extraction of pDNA complexed with DOTMA/Chol/Gal-C4-Chol liposomes was greater than that with control DOTMA/Chol liposomes. A two-compartment dispersion model revealed that both the tissue binding and cellular internalization rate were higher for the DOTMA/Chol/Gal-C4-Chol liposome complexes compared with the control liposome complexes. The tissue binding was significantly reduced by the presence of 20 mM galactose. When their cellular localization in the perfused liver at 30 min postinjection was investigated, it was found that the parenchymal uptake of the DOTMA/Chol/Gal-C4-Chol liposome complexes was greater than that of the control liposome complexes. The parenchymal cell/ nonparenchymal cell uptake ratio was as high as unity.
conclusionGalactosylation of the liposome/pDNA complexes increases the tissue binding and internalization rate via an asialoglycoprotein receptor-mediated process. Because of the large particle size of the complexes (approximately 150 nm), however, penetration across the fenestrated sinusoidal endothelium appears to be limited.
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