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.

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 3µg of antiviral have the same efficiency as a medium containing 30µg 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.