Though the larger spheres also experience greater Selumetinib hydrodynamic forces that disrupts their adhesion. Overall, in light of this robust negative effect of plasma corona on the adhesion of the 330 nm PLGA spheres with an actual size range from,170–500 nm, we would then anticipate that PLGA nanospheres with sizes in the 50– 100 nm range are likely to also exhibit negative adhesion in human blood flow. We are currently working to modify our particle fabrication techniques to obtain PLGA nanoparticles in this size range to confirm this assertion. Finally, though there was no significant donor effect observed with the adhesion of PS spheres in blood relative to buffer flow, the slight reduction in the adhesion of PS particles in the blood of donor A, which consistently conferred the greatest reduction in PLGA adhesion, compared to adhesion of PS in the blood of other donors may suggest that particles of any material type can have their vascular-targeted adhesion negatively impacted at a high enough plasma concentration of the negative proteins in blood. The lack of a significance difference in the PLGA adhesion levels between plasma and whole blood flow assays for low PLGA binding donors suggests that the effect of the adsorbed plasma proteins is large enough in these cases, i.e. high adsorption of critical proteins, to make any blood cell-particle interactions that may impact adhesion level inconsequential. Conversely, the level of adsorption of plasma proteins on PLGA in the blood of high binding donors is likely not as robust such that PLGA adhesion is only mildly affected in the flow of plasma from these donors. However, when particle-blood cell interactions that have previously been reported between microspheres and RBCs and WBCs are present in whole blood flow, it served to further disrupt particle adhesion. This explains the larger reduction in the adhesion of 5 mm spheres in whole blood assays relative to plasma for high binding donors. The distinction between plasma flow adhesion and whole blood adhesion is less pronounced for the smaller spheres evaluated likely due to a reduced effect of blood cell-particle interaction for the smaller sizes. We previously reported that the adhesion of 5 mm spheres are significantly reduced in laminar blood flow as the blood hematocrit, or RBC concentration, is increased from 30 to 45% while the adhesion of nanospheres and small microspheres remain the same or is slightly higher with the same increase in blood hematocrit. Here, the presence of RBCs in flow helps concentrate the smaller particles at the wall relative to plasma flow but with no negative impact from blood cell interactions; hence the higher adhesion of the 330 nm particles in whole blood relative to plasma flows for high binding donors. However, the impact of a higher concentration of the 5 mm spheres at the wall in blood flow on their adhesion would be negated by the cell-particle collisions that tend to disrupt adhesion for this particle size.