Simple mixing of IFN with a polysaccharide having high liver affinity enables IFN to target to the liver.
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.
Tabata
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Y
Institute for Frontier Medical Sciences, Kyoto University, Japan.
Matsui
Y
Y
Uno
K
K
Sokawa
Y
Y
Ikada
Y
Y
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
D002614:Chelating Agents; D005936:Glucans; D007370:Interferon Type I; D011994:Recombinant Proteins; D004369:Pentetic Acid; C009109:pullulan; D015088:2',5'-Oligoadenylate Synthetase; D015032:Zinc