Molecularly Imprinted Hydrogels Selective to Ribavirin as New Drug Delivery Systems to Improve Efficiency of Antiviral Nucleoside Analogue: A Proof-of-Concept Study with Influenza A Virus

Macromol Biosci. 2022 Feb;22(2):e2100291. doi: 10.1002/mabi.202100291. Epub 2021 Nov 21.

Abstract

This study describes the synthesis and evaluation of different imprinted hydrogels using ribavirin as template molecule. Ribavirin serves as a model molecule because it possesses a broad-spectrum antiviral effect against RNA viruses, which are expected as emerging viruses. The choice of monomers enables to stabilize the pre-polymerization complex and to synthesize biocompatible polymers. Predictive studies as well as experimental works conclude similar results on best ribavirin:monomers ratios. Thus, materials exhibit high selective cavities toward ribavirin. These affinities allow to show release profiles drastically different from the non-imprinted ones at two temperatures. The imprinted materials show a sustained profile able to release antiviral for more than 24 h. The hydrogels obtained are biocompatible with model cells retained, human lung epithelial BEAS-2B cells. Cell viability is excellent and pro-inflammatory response is insignificant when imprinted polymers are incubated with cells. Finally, viral tests carried out on Influenza A infected lung cells show that imprinted delivery systems delivering 1 to 3 µg of antiviral have the same efficiency as a medium containing 30 µg mL-1 of active agent. As a very interesting result, the molecularly imprinted polymers as drug delivery systems allow to increase the local concentration of antiviral, to improve their delivery when its bioavailability is low.

Keywords: antiviral nucleoside; controlled release; human bronchial epithelial BEAS-2B cells; hydrogel microparticles; molecularly imprinted polymer; ribavirin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology
  • Drug Delivery Systems
  • Humans
  • Hydrogels / pharmacology
  • Influenza A virus*
  • Molecular Imprinting* / methods
  • Nucleosides
  • Ribavirin / pharmacology

Substances

  • Antiviral Agents
  • Hydrogels
  • Nucleosides
  • Ribavirin