BIOMAT Database Logo BIOMAT Database Logo

Effect of galactose density on asialoglycoprotein receptor-mediated uptake of galactosylated liposomes. 2005

Chittima Managit, and Shigeru Kawakami, and Fumiyoshi Yamashita, and Mitsuru Hashida
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.

Galactosylated (Gal) liposomes containing various molar ratios of cholesten-5-yloxy-N-(4-((1-imino-2-D-thiogalactosylethyl)formamide (Gal-C4-Chol) as a ligand for asialoglycoprotein receptors were prepared to study the effect of the galactose content of Gal-liposomes labeled with [3H]cholesteryl hexadecyl ether on their targeted delivery to hepatocytes. The uptake characteristics of Gal-liposomes having Gal-C4-Chol of 1.0%, 2.5%, 3.5%, 5.0%, and 7.5% were evaluated. The uptake and internalization by HepG2 cells was enhanced by the addition of Gal-C4-Chol to the Gal-liposomes. In the presence of excess galactose, the uptake of Gal-liposomes having Gal-C4-Chol of 3.5%, 5.0%, and 7.5% was inhibited suggesting asialoglycoprotein receptor mediated uptake. After intravenous injection, Gal-liposomes having Gal-C4-Chol of 3.5%, 5.0%, and 7.5%, rapidly disappeared from the blood and exhibited rapid liver accumulation with up to about 80% of the dose within 10 min whereas Gal-liposomes having low Gal-C4-Chol (1.0% and 2.5%) showed a slight improvement in liver accumulation compared with bare-liposomes. Gal-liposomes with high Gal-C4-Chol are preferentially taken up by hepatocytes and the highest uptake ratio by parenchymal cells (PC) and nonparenchymal cells (NPC) (PC/NPC ratio) was observed with Gal-liposomes having of 5.0% Gal-C4-Chol. We report here that the galactose density of Gal-liposomes prepared by Gal-C4-Chol is important for both effective recognition by asialoglycoprotein receptors and cell internalization.

UI MeSH Term Description Entries
D008081 Liposomes Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. Niosomes,Transferosomes,Ultradeformable Liposomes,Liposomes, Ultra-deformable,Liposome,Liposome, Ultra-deformable,Liposome, Ultradeformable,Liposomes, Ultra deformable,Liposomes, Ultradeformable,Niosome,Transferosome,Ultra-deformable Liposome,Ultra-deformable Liposomes,Ultradeformable Liposome
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D010316 Particle Size Relating to the size of solids. Particle Sizes,Size, Particle,Sizes, Particle
D002782 Cholestenes Steroids with methyl groups at C-10 and C-13 and a branched 8-carbon chain at C-17. Members include compounds with any degree of unsaturation; however, CHOLESTADIENES is available for derivatives containing two double bonds.
D004337 Drug Carriers Forms to which substances are incorporated to improve the delivery and the effectiveness of drugs. Drug carriers are used in drug-delivery systems such as the controlled-release technology to prolong in vivo drug actions, decrease drug metabolism, and reduce drug toxicity. Carriers are also used in designs to increase the effectiveness of drug delivery to the target sites of pharmacological actions. Liposomes, albumin microspheres, soluble synthetic polymers, DNA complexes, protein-drug conjugates, and carrier erythrocytes among others have been employed as biodegradable drug carriers. Drug Carrier
D005690 Galactose An aldohexose that occurs naturally in the D-form in lactose, cerebrosides, gangliosides, and mucoproteins. Deficiency of galactosyl-1-phosphate uridyltransferase (GALACTOSE-1-PHOSPHATE URIDYL-TRANSFERASE DEFICIENCY DISEASE) causes an error in galactose metabolism called GALACTOSEMIA, resulting in elevations of galactose in the blood. D-Galactose,Galactopyranose,Galactopyranoside,D Galactose
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor

Related Publications

Chittima Managit, and Shigeru Kawakami, and Fumiyoshi Yamashita, and Mitsuru Hashida
Asialoglycoprotein receptor-mediated gene transfer using novel galactosylated cationic liposomes.
November 1998, Biochemical and biophysical research communications,
Chittima Managit, and Shigeru Kawakami, and Fumiyoshi Yamashita, and Mitsuru Hashida
Effect of gal/GalNAc regioisomerism in galactosylated liposomes on asialoglycoprotein receptor-mediated hepatocyte-selective targeting in vivo.
March 2021, Journal of liposome research,
Chittima Managit, and Shigeru Kawakami, and Fumiyoshi Yamashita, and Mitsuru Hashida
Asialoglycoprotein Receptor-Mediated Gene Delivery to Hepatocytes Using Galactosylated Polymers.
September 2015, Biomacromolecules,
Chittima Managit, and Shigeru Kawakami, and Fumiyoshi Yamashita, and Mitsuru Hashida
Fluorine-18 labeled galactosylated chitosan for asialoglycoprotein-receptor-mediated hepatocyte imaging.
August 2010, Bioorganic & medicinal chemistry letters,
Chittima Managit, and Shigeru Kawakami, and Fumiyoshi Yamashita, and Mitsuru Hashida
Effect of hydrophile-lipophile balance of the linker in Gal/GalNAc ligands on high-affinity binding of galactosylated liposomes by the asialoglycoprotein receptor.
August 2022, International journal of pharmaceutics,
Chittima Managit, and Shigeru Kawakami, and Fumiyoshi Yamashita, and Mitsuru Hashida
Asialoglycoprotein-receptor-targeted hepatocyte imaging using 99mTc galactosylated chitosan.
May 2006, Nuclear medicine and biology,
Chittima Managit, and Shigeru Kawakami, and Fumiyoshi Yamashita, and Mitsuru Hashida
Design and synthesis of novel galactosylated polymers for liposomes as gene drug carriers targeting the hepatic asialoglycoprotein receptor.
April 2008, Journal of drug targeting,
Chittima Managit, and Shigeru Kawakami, and Fumiyoshi Yamashita, and Mitsuru Hashida
Receptor-mediated gene transfer into hepatic cells using asialoglycoprotein-labeled liposomes.
May 1994, Annals of the New York Academy of Sciences,
Chittima Managit, and Shigeru Kawakami, and Fumiyoshi Yamashita, and Mitsuru Hashida
alpha3-galactosylated glycoproteins can bind to the hepatic asialoglycoprotein receptor.
November 2000, European journal of biochemistry,
Chittima Managit, and Shigeru Kawakami, and Fumiyoshi Yamashita, and Mitsuru Hashida
Galactosylated manganese ferrite nanoparticles for targeted MR imaging of asialoglycoprotein receptor.
November 2013, Nanotechnology,
Copied contents to your clipboard!