Uptake and fate of water-soluble, nondegradable polymers with antiviral activity in cells and animals.

Poly(9-vinyladenine) and poly(1-vinyluracil) which are nondegradable, soluble polymers are taken up partially by mammalian cells grown in culture. The polymers remain associated with cells for several generations. In mice, after ip application, polymers slowly accumulate in liver, spleen, and thymus and remain there for as long as a month. Thus, these polymers which suppress the replication of murine leukemia viruses also accumulate in organs where the virus replicates. However, their antiviral activity does not reflect the amount of polymer found in these animal tissues. We propose that the polymers are gradually segregated into a group of cells or into subcellular organelles away from primary sites of virus replication. The results suggest that for a directly acting polymeric drug, a half-life over 24 h is without advantage.