Boronic acid-mediated mucin/surface interactions of zwitterionic polymer brushes

Abstract

Mucus is a substance that acts as a protective barrier, shielding tissues from infections caused by viruses and bacteria. Recent studies highlight the advantages of transmucosal drug delivery compared to traditional delivery methods. However, external particles in mucus struggle to penetrate its deeper layers and are often eliminated by mucus clearance mechanisms, hindering effective drug delivery. To gain a deeper understanding of how material surfaces interact with mucus, we grafted brushes of poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) onto silica surfaces, followed by the straightforward installation of a terminal boronic acid moiety (3-phenylboronic acid, APBA). The modification process was carried out following a surface-initiated activator regenerated by electron transfer atom transfer radical polymerization (SI-ARGET ATRP), a method known for its effectiveness in producing well-defined grafted polymers. After conjugation of APBA, we studied the effects of surface chemistry on properties such as pH-sensitivity and mucin adsorption. The surfaces modified with the zwitterionic polymer showed no mucin interaction regardless of system pH. However, all the surfaces containing the boronic acid showed boronic acid–sialic acid interactions, particularly at lower pH values. The insights gained from this study will enhance our understanding of the interactions between the zwitterionic PMPC and the boronic acid APBA with mucins, laying the groundwork for future chemical modifications of particle surfaces aimed at modulating their transport through mucus.