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KMID : 0545120110210020176
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Journal of Microbiology and Biotechnology
2011 Volume.21 No. 2 p.176 ~ p.182
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Preparation of Branched Dextran Microspheres of Soluble Interferon-alpha and its Activity In Vitro and In Vivo
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Hong Hua
Jo Jeong-Rang
Yeon Ji-Hyeon
Hong Jun-Tack
Jung Kyung-Hwan
Yoo Sun-Kyun
Jang Byeong-Churl
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Abstract
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The study objective was to prepare biodegradable branched dextran microspheres encapsulated with His-tagged interferon-alpha (BDM-hIFN-α) and evaluate its activity in vitro and in vivo. The glycidyl methacrylate derivatized dextrans (Dex-GMA) as precursor was primarily synthesized by substituting hydroxyl groups of either the branched or linear type of dextran with GMA. Dex-GMA microspheres loaded with hIFN-α was then prepared by the water-in? water emulsion technique. In vitro release and Western blotting experiments demonstrated the retained activity of hIFN-α released from branched dextran microspheres at 24 h by inducing phosphorylation of signal transducer and activator transcription-1 (STAT-1), a down-stream effector of IFN-α, in HepG2 cells. Animal data further revealed a peak of plasma levels of IFN-α in rats injected intravenously with BDM-hIFN-α at 10 min post-injection, but a sharp decline at 2 h. High plasma levels of neopterin, a plasma protein induced by IFN-α, were also detected in rats injected with BDM-hIFN-α at 10 min post-injection. Notably, plasma levels of neopterin remained high at 4 h, but largely declined thereafter.
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KEYWORD
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Branched dextran microspheres, IFN-a, p-STAT-1, HepG2, Neopterin
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