title: Simple mixing of IFN with a polysaccharide having high liver affinity enables IFN to target to the liver.
abstract: Interferon (IFN) therapy is only one method that is clinically effective in controlling disease activity in patients with chronic hepatitis. A chelating residue (diethylenetriamine pentaacetic acid, DTPA) was introduced to pullulan, which is a polysaccharide with high liver affinity. This DTPA-pullulan could conjugate with IFN through Zn2+ coordination on mixing these three components. Intravenous injection of the IFN-DTPA-pullulan conjugate with Zn2+ coordination induced activity in the liver of an antiviral enzyme. 2',5'-oligoadenylate synthetase at IFN doses lower than those used for free IFN injection. In addition, synthetase induction by the conjugate continued for a longer time than did induction by free IFN. Liver targeting of IFN by this conjugation technique based on Zn2+ coordination opens a new method of IFN therapy.
authors.affiliation: Institute for Frontier Medical Sciences, Kyoto University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tabata
authors.forename: Y
authors.initials: Y
authors.lastname: Matsui
authors.forename: K
authors.initials: K
authors.lastname: Uno
authors.forename: Y
authors.initials: Y
authors.lastname: Sokawa
authors.forename: Y
authors.initials: Y
authors.lastname: Ikada
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis; D000818:Animals; D002614:Chelating Agents / Q000737:chemistry; D004790:Enzyme Induction; D005260:Female; D005936:Glucans / Q000737:chemistry*; D006521:Hepatitis, Chronic / Q000188:drug therapy* / Q000378:metabolism; D007275:Injections, Intravenous; D007370:Interferon Type I / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D004369:Pentetic Acid / Q000737:chemistry; D011994:Recombinant Proteins; D014018:Tissue Distribution; D015032:Zinc / Q000494:pharmacology
chemical_list: D002614:Chelating Agents; D005936:Glucans; D007370:Interferon Type I; D011994:Recombinant Proteins; D004369:Pentetic Acid; C009109:pullulan; D015088:2',5'-Oligoadenylate Synthetase; D015032:Zinc