Preparation of Branched Dextran Microspheres of Soluble Interferonalpha 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-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.