The Impact of the Plasma Protein Corona on the Adhesion Efficiency of Drug Carriers to the Blood Vessel Wall.

Abstract

Upon injection of vascular-targeted drug carriers into the bloodstream, plasma proteins rapidly coat the carrier surface, forming a plasma protein corona. This corona is dependent on a host of parameters, including physicochemical particle properties and the plasma composition. Although several studies have identified key roles of the protein corona regarding circulation time, clearance, and biodistribution, the role of the plasma protein corona on the adhesion efficiency of vascular-targeted carriers (VTCs) to inflamed human umbilical vein endothelial cells (HUVECs) in human blood flow remains relatively unknown. In this dissertation, it is observed that the plasma protein corona exerts a negative effect on the adhesion of drug carriers in blood flow; however, the extent of these observations depend on a host of parameters including drug carrier material type, targeting ligand density, flow profile, plasma exposure time, and plasma anticoagulant. Furthermore, the magnitude of the corona-induced negative adhesion effects is shown to be heavily linked to the adsorption of immunoglobulin antibodies in plasma. This work has a variety of important implications for the intelligent design of VTCs. First, the fact that immunoglobulins heavily dictate adhesion reduction of drug carriers offers insight into specific directions to limit the effects of the protein corona. Specifically, tuning the corona to avoid adsorption of these proteins or coating with non-fouling dysopsonin proteins offers a method to maintain targeting efficiency in the presence of corona formation. Second, this work may explain why current targeted drug delivery systems often exhibit poor accumulation to the target site based on the large reduction of particles upon exposure to human plasma. Third, this work could be used to develop strategies to predict or diagnose a specific drug carrier based on its protein corona profile, hopefully leading to more successful translations of drug delivery systems to the market. Overall, this work shows that protein corona is a critical parameter when designing high-efficient targeted drug carriers and may be exploited or eliminated to achieve maximum adhesion specificity in vivo.