Influence of particle z‐potential and experimental procedure on protein corona formation and multicomponent aggregation

Abstract Drug delivery systems have renewed attention in recent years to achieve targeted delivery while decreasing toxic side effects. However, there are many factors that prevent optimal administration of drug delivery particles. For instance, protein corona formation and aggregation both decrease the circulation half‐life of drug delivery particles, leading to sequestration to the liver and spleen. Therefore, optimal surface modifications are needed to decrease protein corona formation and avoid aggregation. In this work, polystyrene particles were modified with multi‐arm and linear polyethylene glycol (PEG) to determine their aggregation profiles and protein corona formation. Multi‐arm PEGs were found to aggregate more than linear PEGs, due to the change in zeta potential from unreacted end groups, which may lead to shorter circulation half‐lives. Furthermore, the protein corona formation and composition were studied after different washing procedures, highlighting the importance of studying protein corona formation with undiluted blood plasma.