Effect of Galactose Density on Asialoglycoprotein Receptor-Mediated Uptake of Galactosylated Liposomes
| Autor: | Shigeru Kawakami, Mitsuru Hashida, Chittima Managit, Fumiyoshi Yamashita |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Time Factors media_common.quotation_subject Pharmaceutical Science Asialoglycoprotein Receptor Tritium Mice chemistry.chemical_compound Cell Line Tumor polycyclic compounds medicine Animals Humans Tissue Distribution Particle Size Internalization media_common Drug Carriers Liposome Cholestenes Galactose Ligand (biochemistry) Molecular biology In vitro medicine.anatomical_structure Liver chemistry Biochemistry Area Under Curve Hepatocyte Liposomes Hepatocytes lipids (amino acids peptides and proteins) Asialoglycoprotein receptor Drug carrier |
| Zdroj: | Journal of Pharmaceutical Sciences. 94:2266-2275 |
| ISSN: | 0022-3549 |
| DOI: | 10.1002/jps.20443 |
| Popis: | 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 [ 3 H]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. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association |
| Databáze: | OpenAIRE |
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