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 ribavirinmonomers 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.