title: Target specific hyaluronic acid-interferon alpha conjugate for the treatment of hepatitis C virus infection.
abstract: Interferon alpha (IFNα) conjugated with polyethylene glycol (PEG) has been widely used for the treatment of hepatitis C virus (HCV) infection as a once-a-week injection formulation. However, the PEGylated IFNα has a low efficacy of ca. 39% and a side effect after repeated injections possibly due to the non-specific delivery with PEGylation. In this work, target specific long-acting hyaluronic acid-interferon alpha (HA-IFNα) conjugate was successfully developed for the treatment of HCV infection. HA-IFNα conjugate was synthesized by coupling reaction between aldehyde modified HA and the N-terminal group of IFNα. The IFNα content could be controlled in the range of 2-9 molecules per single HA chain with a bioconjugation efficiency higher than 95%. According to in vitro anti-proliferation assay using Daudi cells, HA-IFNα conjugate showed a comparable biological activity to PEG-Intron. In vivo real-time bioimaging confirmed the target specific delivery of near-infrared fluorescence (NIRF) dye labeled HA-IFNα conjugate to the liver in mice. In addition, pharmacokinetic analysis revealed the enhanced residence time longer than 4 days. After tail-vein injection, HA-IFNα conjugate induced ca. 60% higher expression of 2',5'-oligoadenylate synthetase 1 (OAS 1) for innate immune responses to viral infection in the murine liver tissues than IFNα and PEG-Intron.
authors.affiliation: Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), San 31, Hyoja-dong, Nam-gu, Pohang, Kyungbuk 790-784, Korea.
authors.forename: Jeong-A
authors.initials: JA
authors.lastname: Yang
authors.forename: Kitae
authors.initials: K
authors.lastname: Park
authors.forename: Hyuntae
authors.initials: H
authors.lastname: Jung
authors.forename: Hyemin
authors.initials: H
authors.lastname: Kim
authors.forename: Sung Woo
authors.initials: SW
authors.lastname: Hong
authors.forename: Seung Kew
authors.initials: SK
authors.lastname: Yoon
authors.forename: Sei Kwang
authors.initials: SK
authors.lastname: Hahn
mesh_terms: D000818:Animals; D002240:Carbohydrate Sequence; D002850:Chromatography, Gel; D005260:Female; D005453:Fluorescence; D006526:Hepatitis C / Q000188:drug therapy*; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016898:Interferon-alpha; D006820:Hyaluronic Acid