The Impact of Anti-Coagulant in Modulating Vascular-Targeted Drug Carrier (VTC) Adhesion Efficiency in Human Blood Flow
Daniel J. Sobczynski and Omolola Eniola-Adefeso
Anti-coagulants are commonly used to preserve whole blood or plasma for storage, in vitro diagnostics, or performing in vitro assays involving blood. The choice of anticoagulant or the absence of it (as in preparation of human serum) is known to influence the proteomic profile of the plasma. In addition, it is known that plasma protein adsorption can have negative effects on vascular-targeted drug carrier (VTC) adhesion. In this work, this phenomenon is explored deeper by considering the impact of the choice of anti-coagulant or absence of it during the preparation of human blood for VTC vascular wall adhesion assays. In particular, a parallel-plate flow chamber assay is used to simulate human blood flow over activated endothelial cells and directly measure VTC binding efficiency of PLGA, silica, and polystyrene nanoparticles. It is observed that for all VTCs tested, adhesion levels in RBC-containing serum flow are drastically reduced relative to citrated plasma, and for polystyrene spheres, adhesion in heparinized whole blood is significantly reduced compared to PLGA and silica spheres. Furthermore, the absence of anticoagulant in non-citrated whole blood re-creates the low adhesion effects seen in RBC-containing serum flow. Overall, the choice of anti-coagulant can modulate VTC adhesion and potentially overestimate VTC adhesion efficiency in vivo where anticoagulant is not present. Instead, our results suggest suspension of human RBCs in serum may be a better model for evaluating VTC functionality for human use.