Selective Targeting of Antiviral and Immunomodulating Agents in the Treatment of Arenavirus Infections.
Abstract
The therapeutic value of large negatively charged liposomes as vehicles for the delivery of antiviral or immunostimulatory agents to the lungs of mice infected with herpes simplex (HSV-1) or influenza virus was examined. Both liposome encapsulated and non-encapsulated ribavirin or muramyl tripeptide were compared for their ability to: i) deposite in pulmonary tissue following intraveneous administration; ii) reduce virus replication in primary target organs; and iii) protect against lethal virus infections. Liposome carriers provided better lung delivery than did non-encapsulated drug. Moreover, liposome encapsulated MTP (L-MTP) was superior to free MTP in activating alveolar macrophage functions as determined by in vitro functional analysis (e.g. phagocytosis, microbicidal and tumoricidal activities), and in protecting mice against intranasal challenge with 10 LD50 of HSV-1. Similarly, intravenous administration of liposome encapsulated ribavirin (L-RIB) (3 mg/mouse) several hours after infection was more effective than free RIB (10 mg/mouse) in protecting mice against intranasal challenge with 10 LD50 of influenza virus. Neither L-RIB nor free RIB was effective in treating HSV-1 infections even though HSV is susceptible to this antiviral agent in vitro (MIC50=30ug/ml). However, combination therapy using both L-RIB and L-MTP was more effective than either agent alone in protecting mice from lethal HSV-1 infection. (Keywords; Liposomes; Ribavirin; Muramyl Tripeptide; Viral Pneumonitis; Drug Synergism; Immunostimulation; Pulmonary Immjunity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 30, 1985
- Accession Number
- ADA178104
Entities
People
- J. D. Gangemi
Organizations
- University of South Carolina