Macromolecular Prodrugs for Controlled Delivery of Ribavirin

Abstract

Ribavirin (RBV)-containing polymers are synthesized based on poly(N-vinylpyrrolidone) and poly(acrylic acid), two polymers with extensive characterization in biomedicine. The copolymers are shown to exhibit a minor to negligible degree of association with erythrocytes, thus effectively eliminating the origin of the main side effects of RBV. The therapeutic benefit of macromolecular RBV prodrugs is illustrated by matched efficacy in suppressing production of nitric oxide by stimulated cultured macrophages as compared to pristine RBV with no associated cytotoxicity, which is in stark contrast to an RBV-based treatment which results in a significant decrease in cell viability. These results contribute to the development of antiviral polymer therapeutics and delivery of RBV in particular.

Highly Active Macromolecular Prodrugs Inhibit Expression of the Hepatitis C Virus Genome in the Host Cells

“…Using this tool, we designed MPs of RBV with potency near matching that of the pristine drug yet without associated toxicity. Together with our previous reports on hemocompatibility of MPs of RBV, our efforts establish a novel platform for safe and efficient delivery of RBV that can also be adapted to other nucleoside analogue drugs for various therapies (antiviral, anticancer).…”

Macromolecular prodrugs of ribavirin: towards a treatment for co-infection with HIV and HCV

“…23,25 In short, human red blood cells (RBC) were obtained from Skejby Hospital blood bank, cryopreserved in 54.7 mM glycerol, 0.050 M NaPO 3 , 0.37 mM NaCl, and on the day of experiment washed in PBS (3 × 10 mL, 5 min, 400 rpm). In a 96-well round-bottomed multiplate, RBCs (45 μL) were subjected to polymers (5 μL) and incubated 24 h (37 °C, 300 rpm).…”

Advanced Prodrug Strategies in Nucleoside and Non-Nucleoside Antiviral Agents: A Review of the Recent Five Years

“…Kryger et al documented the synthesis of two macromolecular prodrugs by polymerization of RBV-acrylate once with poly(acrylic acid) (AA) [ 53 ] and another with poly( N -vinylpyrrolidone) (NVP) [ 54 ] (see 16 and 17 in Figure 9 , respectively). The resulting prodrugs showed no cytotoxicity to macrophages.…”