Zwitterionic polymer grafted from silica surface for the study of mucosal transport

Mucus is a complex viscoelastic and adhesive substance which serves as a dynamic barrier that protects tissue against infection and invasion by viruses and bacteria. Recently, transmucosal drug delivery has shown promising advantages over other existing delivery routes, including improved bioavailability and therapeutic effects. However, particles with low diffusivities in mucus cannot reach deep mucus layers and are eliminated by mucus clearance mechanism, causing an impediment for drug delivery. It is also known that zwitterionic polymers (ZW) including poly(carboxybetaine) (PCB) or poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) moiety have good mucopenetration properties. Despite that, fundamental studies and understanding of specific and non-specific interactions between mucus and ZW polymers are still lacking. On the other hand, boronic acids have been used as mucoadhesive components in delivery systems due to their ability to form high-affinity complexes with 1,2-diols such as sialic acids present in mucus. Herein, we studied the interactions between mucus and zwitterionic polymers with PMPC, and the combined effects of boronic acid chemistry, surface presentation, and pH on particle-mucus interactions. We optimized the grafting synthesis of ZW polymers from glass slides and silica particles as well as the further functionalization with different boronic acids. Surface characterization is done by XPS, contact angle, ellipsometry, DLS, SEM and TGA.