Small Interfering RNA Nunchucks with a Hydrophobic Linker for Efficient Intracellular Delivery

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.