title: Design for cell-specific targeting of proteins utilizing sugar-recognition mechanism: effect of molecular weight of proteins on targeting efficiency.
abstract: Hepatic targeting of proteins utilizing the sugar-recognition mechanism was investigated in mice after intravenous injection. Five proteins with different molecular weights, i.e., bovine gamma-globulins (IgG), bovine serum albumin (BSA), recombinant human superoxide dismutase (SOD), soybean trypsin inhibitor (STI), and chicken egg white lysozyme (LZM), were modified with 2-imino-2-methoxyethyl 1-thiogalactoside to obtain galactosylated proteins (Gal-IgG, Gal-BSA, Gal-SOD, Gal-STI, and Gal-LZM). The numbers of galactose residues were 38, 20, 11, 6, and 5 for Gal-IgG, Gal-BSA, Gal-SOD, Gal-STI, and Gal-LZM, respectively. All galactosylated proteins were dose-dependently taken up by the liver and the relative amount accumulated in the liver was decreased with an increase of the administered dose. At low doses (0.05 and 0.1 mg/kg), Gal-IgG, Gal-BSA, and Gal-SOD could be taken up by the liver up to more than 70-80% of dose within 10 min after intravenous injection, but the maximum amounts accumulated in the liver were approximately 40 and 30% of the dose for Gal-STI and Gal-LZM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Drug Delivery Research, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nishikawa
authors.forename: H
authors.initials: H
authors.lastname: Hirabayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Takakura
authors.forename: M
authors.initials: M
authors.lastname: Hashida
mesh_terms: D000818:Animals; D050260:Carbohydrate Metabolism; D016503:Drug Delivery Systems; D015195:Drug Design; D005690:Galactose / Q000378:metabolism; D005919:Glomerular Filtration Rate; D007205:Indium Radioisotopes; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008970:Molecular Weight; D011506:Proteins / Q000378:metabolism* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D007205:Indium Radioisotopes; D011506:Proteins; D005690:Galactose