Presented to the EC monolayer by the spheres also advantage their binding relative to the smaller spheres

Nanospheres of different metal oxides having the same size and surface charge adsorb different plasma proteins. We also find that the negative effect of plasma proteins on the adhesion of PLGA particles in blood flow was persistent for all particle sizes explored, from 5 mm down to 330 nm despite previous report of particle size affecting the quantity and quality of proteins in the corona of nanoparticles. This lack of a major effect of PLGA particle size on their blood flow adhesion to ECs in this work may be due to the affinity of the relevant plasma proteins for PLGA surfaces not being significantly Reversine affected within the range of particle size explored. Indeed, about a third or more of plasma proteins in the corona of ultra small nanoparticles are reported to be conserved with changes in particle size. Our results show that the extent of the negative adhesion effect of plasma proteins on PLGA particles is donor dependent, particularly for the largest spherical size evaluated. This “donor effect” is likely linked to variation in plasma protein composition, type and amount of individual proteins, across different individuals, which results in different levels of the “critical” proteins being absorbed on PLGA particles when exposed to different donor blood. Indeed, recent studies have reported the existence of significant plasma protein diversity within the general human population, irrespective of gender and ethnic background. As such, we postulate that PLGA particles in the blood of low binding donors acquire a higher amount of the critical plasma proteins, due to higher abundance of these proteins, which leads to a greater reduction in their EC adhesion in the flow of plasma from these donors than observed in the plasma of high binding donors. This assertion is supported by the observation of a thicker protein band at the 150 kDa protein mark on the SDS-PAGE gel for the corona stripped from 5 mm PLGA particles soaked in plasma from a low binding donor compared to the corona obtained from ones soaked in plasma from a high binding donor. The significantly lower adhesion of the 330 nm spheres in the plasma flow of high binding donors relative to adhesion in viscous buffer versus the lack of a plasma protein impact on the adhesion of 5 mm spheres in the plasma flow of the same high binding donors relative to viscous buffer would suggest that effect of plasma proteins on particle adhesion is more pronounced for the smaller spheres. As aforementioned, protein adsorption processes are the result of thermodynamic gradients that depend on the space available, e.g. particle size, for adsorption to take place. As such, it is likely that the distinction between a high and a low binding donor in terms of plasma protein concentration is less impactful when there is a small surface area for adsorption. However, it is also possible that the larger surface area for contact, and hence more copies of targeting ligand.