期刊
BIOMATERIALS
卷 32, 期 33, 页码 8722-8729出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2011.07.088
关键词
Hyaluronic acid; Interferon alpha; Conjugate; Targeted delivery; Hepatitis C virus
资金
- Converging Research Center through the National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology [2009-0081871]
- Ministry of Health & Welfare, Republic of Korea [A080711]
- Korea Health Promotion Institute [A080711] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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.
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