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Target specific hyaluronic acid–interferon alpha conjugate for the treatment of hepatitis C virus infection

Paper ID Volume ID Publish Year Pages File Format Full-Text
7265 542 2011 8 PDF Available
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.

Keywords
Hyaluronic acid; Interferon alpha; Conjugate; Targeted delivery; Hepatitis C virus
First Page Preview
Target specific hyaluronic acid–interferon alpha conjugate for the treatment of hepatitis C virus infection
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 33, November 2011, Pages 8722–8729
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering