Development of Cell-Specific Targeting Systems for Drugs and Genes

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概要

• 論文の詳細を見る

• Cell-specific targeting systems for drugs and genes have been developed by using glycosylated macromolecule as a vehicle that can be selectively recognized by carbohydrate receptors. Pharmacokinetic analyses of the tissue distribution of glycosylated proteins came to the conclusion that the surface density of the sugar moiety on the protein derivative largely determines the binding affinity for the receptors and plasma lectin. Many glycosylated delivery systems have been developed and their usefulness investigated in various settings. Galactosylated polymers, when properly designed, were found to be effective in delivering prostaglandin E_1 and other low-molecular-weight drugs selectively to hepatocytes. In addition, glycosylated superoxide dismutase and catalase were successfully developed with minimal loss of enzymatic activity. A simultaneous targeting of these two enzymes to liver nonparenchymal cells significantly prevented hepatic ischemia/reperfusion injury. On the other hand, galactosylated catalase, a derivative selectively delivered to hepatocytes, effectively inhibited hepatic metastasis of colon carcinoma cells in mice. Finally, hepatocyte-targeted in vivo gene transfer was achieved by synthesizing a multi-functional carrier molecule, which condenses plasmid DNA, delivering DNA to hepatocytes through recognition by asialoglycoprotein receptors, and releasing DNA from endosomes/lysosomes into cytoplasm.

• 公益社団法人日本薬学会の論文
• 2005-02-01

著者

• Nishikawa Makiya

  Department Of Biopharmaceutics And Drug Metabolism Graduate School Of Pharmaceutical Science Kyoto U

• Nishikawa Makiya

  京都大学 薬学研究科病態情報薬学

• Nishikawa Makiya

  Department Of Biopharmaceutics And Drug Metabolism Graduate School Of Pharmaceutical Sciences Kyoto

関連論文

• Analysis of Hepatic Disposition of Native and Galactosylated Polyethylenimine Complexed with Plasmid DNA in Perfused Rat Liver
• Pharmacokinetic considerations regarding non-viral cancer gene therapy
• Pharmacokinetic Evaluation of Biodistribution Data Obtained with Radiolabeled Proteins in Mice
• Pharmacokinetic Analysis of the in Vivo Disposition of Chemically Modified Proteins in Rats : Effect of Radiolabeling Method
• Role of Tyrosine and Tryptophan in Chemically Modified Serum Albumin on Its Tissue Distribution(Biopharmacy)
• Effects of Methyl-β-cyclodextrin Treatment on Secretion Profile of Interferon-β and Zonula Occuludin-1 Architecture in Madin–Darby Canine Kidney Cell Monolayers
• Secretion Mode and Subcellular Localization of Human Interferon-β Exogenously Expressed in Porcine Renal Epithelial LLC-PK_1 Cells(Biopharmacy)
• Unique Cytokine Production Profile Following Stimulation with DNA in Macrophages from NZB/W F_1 Mice(Miscellaneous)
• Hydrogen peroxide-mediated nuclear factor κB activation in both liver and tumor cells during initial stages of hepatic metastasis
• Influence of Cholesterol Composition on the Association of Serum Mannan-Binding Proteins with Mannosylated Liposomes(Analytical Biochemistry)
• Tissue-specific in vivo gene transfer characteristics following direct injection of plasmid DNA
• Nonviral Approaches Satisfying Various Requirements for Effective in Vivo Gene Therapy
• Enhancement of antiproliferative activity of interferons by RNA interference-mediated silencing of SOCS gene expression in tumor cells
• Development of Cell-Specific Targeting Systems for Drugs and Genes
• Histogram Analysis of Pharmacokinetic Parameters by Bootstrap Resampling from One-point Sampling Data in Animal Experiments

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