Target specific hyaluronic acid-interferon alpha conjugate for the treatment of hepatitis C virus infection
SCIE
SCOPUS
- Title
- Target specific hyaluronic acid-interferon alpha conjugate for the treatment of hepatitis C virus infection
- Authors
- Yang, JA; Park, K; Jung, H; Kim, H; Hong, SW; Yoon, SK; Hahn, SK
- Date Issued
- 2011-11
- Publisher
- ELSEVIER
- Abstract
- Interferon alpha (IFN alpha) 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 IFN alpha has a low efficacy of ca. 39% and a side effect after repeated injections possibly due to the nonspecific delivery with PEGylation. In this work, target specific long-acting hyaluronic acid-interferon alpha (HA-IFN alpha) conjugate was successfully developed for the treatment of HCV infection. HA-IFN alpha conjugate was synthesized by coupling reaction between aldehyde modified HA and the N-terminal group of IFN alpha. The IFN alpha 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-IFN alpha 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-IFN alpha conjugate to the liver in mice. In addition, pharmacokinetic analysis revealed the enhanced residence time longer than 4 days. After tail-vein injection, HA-IFN alpha 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 IFN alpha and PEG-Intron. (C) 2011 Elsevier Ltd. All rights reserved.
- Keywords
- Hyaluronic acid; Interferon alpha; Conjugate; Targeted delivery; Hepatitis C virus; PROTEIN; DELIVERY; RECEPTOR; CD44; IDENTIFICATION; PEGYLATION; RIBAVIRIN; PEPTIDE; FORM
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/17039
- DOI
- 10.1016/J.BIOMATERIALS.2011.07.088
- ISSN
- 0142-9612
- Article Type
- Article
- Citation
- BIOMATERIALS, vol. 32, no. 33, page. 8722 - 8729, 2011-11
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