Enhanced cytocompatible gelatin/chondroitin sulfate/ionic liquid polyelectrolyte multilayers with virucidal activity against mouse hepatitis coronavirus

The cytotoxicity of ionic liquids (ILs) in solution, including aqueous 1-n-hexadecyl-3-methylimidazolium chloride (C16MImCl), 1-n-hexadecyl-3-methylimidazolium methane sulfonate (C16MImMeS), and 1-n-hexadecyl pyridinium chloride monohydrate (C16PyrCl⋅H2O) solutions and polyelectrolyte multilayers (PEMs) containing ILs were investigated against mouse hepatitis virus (MHV-3) and fibroblast cells (L929). C16MImMeS and C16PyrCl⋅H2O exhibited virucidal activity against MHV-3 after 30 s of exposure at 662.31 nM and 744.88 nM, respectively. However, these ILs demonstrated considerable toxicity against fibroblast cells (2.0 × 105 cells/well) at 583 nM (C16MImCl), 498 nM (C16MImMeS), and 559 nM (C16PyrCl⋅H2O), limiting their direct application in aqueous solutions. Therefore, these ILs were combined with PEMs consisting of alternating 15 layers of gelatin (GE) and chondroitin sulfate (CS) to address this limitation. The PEMs were deposited on oxidized poly(ethylene terephthalate) (PET) using the layer-by-layer (LbL) approach. The ILs altered the relative surface adhesion force, reducing it from 4.08 nN on GE/CS PEM to the range between 2.23 and 3.10 nN on the GE/CS IL PEMs. The ILs enhanced surface electrostatic forces while decreasing adhesion forces on the surfaces. Incorporating ILs into the PEMs proved a promising strategy as they reduced the toxicity of the ILs towards L929 cells while maintaining their virucidal efficacy. The GE/CS PEM without IL did not exhibit virucidal activity against MHV-3. In contrast, GE/CS PEMs combined with C16MImMeS showed virucidal activity after 24 h, inactivating 99.99 % of the virus. The PEMs associated with the ILs were cytocompatible toward the L929 cells after a 48-hour incubation period. GE/CS IL PEMs hold promise as cytocompatible surface coatings for solid materials due to their durability and ability to prevent viral growth.