Antifouling surface for biomedical devices: Modification of COC surface by quaternary ammonium moieties via diazonium chemistry

Abstract

Prefilled biomedical devices (PFD) are growing in the pharmaceutical market due to the ease of delivering a precise dose of protein drugs. As an appealing alternative to the fragile glass, cyclic olefin copolymer (COC) was suggested. However, in the case of COC, the stability of the drug may be negatively impacted by protein aggregation. To potentially improve the surface properties of COC for PFDs, we performed functionalization of COC with quaternary ammonium moieties (QAS) using the advantages of diazonium surface chemistry. The successful functionalization of COC using QAS-diazonium salts (QAS-DS) with different alkyl chain lengths (C4, C8, C9, C10, C12) was confirmed by Raman spectroscopy and XPS measurements. Optical and fluorescence measurements revealed the optimal length of the alkyl chain-COC-C4 for improved antibiofouling performance towards bovine serum albumin (BSA). Moreover, in contrast to glass, polypropylene (PP), and pristine COC, COC-C4 allows storing the insulin for at least 2 weeks without the changes in protein structure according to dynamic light scattering and TEM images. Additionally, diazonium functionalization allows for conserving the high permeability resistance, transparency, and mechanical stiffness. The improved stability of insulin in a COC-C4 container is explained by the formation of an additional hydration layer serving as a barrier to undesired interaction with biomolecules.