Enhancement of Antiviral Agents Through the Use of Controlled-Release Technology.

Abstract : This First Annual Progress Report covers research completed during the period from November 1, 1985, through January 31, 1987. The major objectives of this research program are a) To develop a programmed-release delivery system (microcapsule system) designed to enhance the immunogenic potential of an inactivated (killed) Japanese Encephalitis (JE) virus vaccine, allowing for immunization against this viral agent and, b) To develop controlled-release microcapsule delivery systems that will enhance the effects of the following immune modulators and antiviral agents: muramyl tripeptide (MTP), interferon (IFN), and poly(riboinosinic acid-ribocytidylic acid) (poly(I.C)). More specifically, we are involved in the development of biocompatible, biodegradable, controlled-release microcapsule formulation to release poly(I.C), interferon (IFN), and JE vaccine at controlled rates after a single intramuscular or intravenous administration. We also plan to develop microcapsule formulations that will target the release of MTP to macrophages, causing macrophage activation and subsequent nonimmune protection against active viral infections. We have prepared and characterized four batches of poly(DL-lactide-co-glycolide) to be used as the polymeric excipients in the microencapsulation work. In addition, we have actively pursued development and testing of poly(I.C) and Je vaccine microcapsule formulations.