title: Preparation of branched dextran microspheres of soluble interferon-alpha and its activity in vitro and in vivo.
abstract: The study objective was to prepare biodegradable branched dextran microspheres encapsulated with His-tagged interferon-alpha (BDM-hIFN-alpha) 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-alpha was then prepared by the water-in-water emulsion technique. In vitro release and Western blotting experiments demonstrated the retained activity of hIFN-alpha 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-alpha, in HepG2 cells. Animal data further revealed a peak of plasma levels of IFN-alpha in rats injected intravenously with BDM-hIFN-alpha at 10 min post-injection, but a sharp decline at 2 h. High plasma levels of neopterin, a plasma protein induced by IFN-alpha, were also detected in rats injected with BDM-hIFN-alpha at 10 min post-injection. Notably, plasma levels of neopterin remained high at 4 h, but largely declined thereafter.
authors.affiliation: Department of Medical Genetic Engineering, Keimyung University School of Medicine, Daegu 700-712, Korea.
authors.forename: Hua
authors.initials: H
authors.lastname: Hong
authors.forename: Jeong Rang
authors.initials: JR
authors.lastname: Jo
authors.forename: Ji-Hyeon
authors.initials: JH
authors.lastname: Yeon
authors.forename: Jun Tack
authors.initials: JT
authors.lastname: Hong
authors.forename: Kyung-Hwan
authors.initials: KH
authors.lastname: Jung
authors.forename: Sun Kyun
authors.initials: SK
authors.lastname: Yoo
authors.forename: Byeong-Churl
authors.initials: BC
authors.lastname: Jang
mesh_terms: D000818:Animals; D002460:Cell Line; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D003911:Dextrans / Q000737:chemistry / Q000378:metabolism*; D004337:Drug Carriers / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D016898:Interferon-alpha / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D008863:Microspheres; D010949:Plasma / Q000737:chemistry; D011485:Protein Binding; D051381:Rats; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D003692:Delayed-Action Preparations; D003911:Dextrans; D004337:Drug Carriers; D007155:Immunologic Factors; D016898:Interferon-alpha