Influence of Phospholipid Composition on Protein Adsorption to Lipid-Coated Silica Microparticles

Silica particles are promising multifunctional drug delivery platforms; however, when in contact with blood or other biological fluids, proteins rapidly adsorb to their surface, forming the protein corona that modulates their biological interactions. In this study, silica microparticles were coated with lipid bilayers using two approaches: the lipid film hydration method and the on-particle solvent-assisted lipid coating (OPSALC) technique. We investigated how phospholipids with varying charges (zwitterionic, anionic, and cationic) and membrane phase influence coating formation and protein corona adsorption. The coating coverage and aggregation were characterized by fluorescence microscopy. The lipid film hydration method enabled coating with a broad range of lipids, but was highly dependent on the membrane phase and electrostatic interactions between lipid head group and particle surface. Pure anionic coatings were not achievable with this method; however, when combining the OPSALC method with a pre-silanization step, fully anionic coatings of silica microparticles were successfully obtained. Assessment by SDS-PAGE revealed differences in protein corona profiles modulated by the lipid compositions on the particles' coatings. Overall, this study highlights the dependence of coating formation and protein corona composition on the phospholipid coatings' properties.