Selective Targeting of Antiviral and Immunomodulating Agents in the Treatment of Arenavirus Infections
Annual rept. 1 Jul 1986-30 Jun 1987; Final rept. 1 Jul 1984-30 Jun 1987
SOUTH CAROLINA UNIV COLUMBIA SCHOOL OF MEDICINE
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Large multilamellar liposomes were used as a delivery vehicle for the antiviral, ribavirin, and the macrophage activator, muramyl tripeptide MTP-PEO. The data presented confirms previous observations on the altered tissue RES and cellular macrophage disposition of intravenously administered drugs and provides evidence to support the therapeutic potential of liposomes in therapy of arenavirus, bunyvirus, orthomyxovirus and herpesvirus infections. Encapsulation of MTP-PE into liposomes enhanced this drugs ability to activate peritoneal, alevolar and liver macrophage antiviral functions. In addition, liposome-encapsulated MTP-PE reduced virus replication in target organs and protected mice from viral infections in which the liver or lung served as the primary site of virus infection. Liposome-encapsulated ribavirin was more effective than free drug in mice infected with influenza virus and in guinea pigs infected with influenza virus and in guinea pigs infected with Pichinde virus. Moreover, the combination of both ribavirin and MTP-PE was superior to either drug alone in the treatment of HSV-1 and Pichinde virus infections. Additional studies have indicated that liposomes can provide a vehicle in which both virustatic and immunomodulating agents can be simultaneously delivered to the same call and thus promote drug synergism. Keywords Antiviral Immunomodulators Liposomes Large multilamellar vesicles Arenavirus Bunyvirus Orthomyxovirus Herpesvirus Ribavirin Myramyl tripeptide MPT-PE Drug carriers Targeted drug delivery Combination therapy RAI.