Selective Targeting of Antiviral and Immunomodulating Agents in the Treatment of Arenavirus Infections
Abstract
The studies presented in this report further document the ability of liposome-encapsulation to augment the immunopotentiating and therapeutic properties of the synthetic immunomodulator, muramyl tripeptide (MTP-PE). Encapsulation of MTP-PE into large negatively charged liposomes enhanced this drugs ability to activate peritoneal, alveolar, and liver macrophage antiviral functions. Moreover, liposome-encapsulation of MTP-PE reduced virus replication in target organs and provided better protection in murine models of herpes simplex type 1 (HSV-1) pneumonitis and hepatitis. In contrast, uncapsulated MTP-PE was more effective than liposome-encapsulated MTP-PE in augmenting resistance to HSV-1 induced encephalitis; thus, free MTP-PE crossed the blood brain barrier and activated either the humoral and/or cellular components of CNS immunity. Liposome delivery of MTP-PE together with the broad spectrum antiviral ribavirin, was examined in guinea pigs lethally infected with Pichinde virus. Guinea pigs receiving either free or liposome-encapsulated ribavirin survived longer and had less virus in target organs than did untreated animals. The data confirm and extend our previous observations that liposomes can enhance the therapeutic potential of antiviral agents in those diseases in which the reticuloendothelial system is involved. In addition, the combination of both liposome-encapsulate MTP-PE and ribavirin appears to be highly effective in arenavirus infections in which both visceral organs and the central nervous system are involved. Keywords: Liposomes; Ribavirin; Pulmonary immunity; CNS immunity; Viral hepatitis; Alveolar macrophages.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 30, 1986
- Accession Number
- ADA217417
Entities
People
- J. D. Gangemi
Organizations
- University of South Carolina