Inhibition of cytomegalovirus late antigen expression and cytomegalovirus replication in human fibroblasts and differentiated monocytic cells by liposome-encapsulated foscarnet

Abstract

Foscarnet is one of the drugs of choice for the treatment of cytomegalovirus (CMV) infections, but its efficacy is limited by systemic toxicity, poor penetration into cells and a short plasma half-life. In this study, two types of sized, foscarnet-containing liposomes were evaluated with respect to their in vitro efficacy against human CMV in differentiated monocytic (THP-1) cells and embryonic lung fibroblasts. Both preparations of liposomal foscarnet inhibited CMV replication and CMV late antigen expression in either cell type. In contrast to free foscarnet, the extent of inhibition was dependent on the cell type, with superior activity towards CMV in THP-1 cells. The antiviral effect was most likely mediated by direct association of liposome-encapsulated foscarnet with THP-1 cells. Free foscarnet, however, showed an equal or greater antiviral activity than liposome-encapsulated foscarnet. At the IC 50 concentrations of free and liposome-encapsulated foscarnet, toxicity towards the permissive cells was not observed. Together with our previous findings of the prolonged circulation time of one of the liposome preparations used in this study, these results indicate that liposome-encapsulated foscarnet warrants further exploration to assess its potential for the treatment of CMV-infections.