389459 Effect of Variation in Hemorheology Between Human and Animal Blood on the Binding Efficacy of Spherical Vascular-Targeted Drug Carrier
To date vascular-targeted carriers (VTCs) for drug delivery have been investigated for therapeutic intervention in several human diseases. Animal models are used extensively in experimental research to evaluate the in vivo utility of VTCs, including in the fields of imaging and drug delivery. However, few of these studies have considered the differences in the hemorheology between common animal models and human blood, and how this would affect the extrapolation of the generated data to human physiology. In particular, no other study to out knowledge has investigated the effect of the differences in blood cell properties (i.e. size, shape and deformability) in VTCs efficacy. This would be of particular importance for drug delivery applications where VTCs must navigate through the red blood cells’ (RBCs) flow to localize and adhere to the endothelial wall.
The present study aims to elucidate the role of RBC dimension in dictating the binding efficiency of spherical particles of various sizes in different blood flow patterns. Specifically, we evaluated the adhesion of inflammation-targeted polystyrene spheres (0.2, 0.5, 2 and 5 μm in diameter) to inflamed endothelial cells using human, mouse, rabbit, pig and cow models. We ran physiological relevant flows in a parallel plate flow chamber (PPFC), first using RBCs-in-buffer flow at fixed 40 %Hct and, second, with whole blood flow. Overall, our results show that the binding capacity of VTCs is significantly influence by blood flow types and most importantly, RBC size.
Result and Discussion
The results showed that the binding efficiency of particles varies with the dimension of RBCs corresponding to different animal models and flow types. We also suggested that the ratio of particle to red blood cell size has significant influences on the margination of vascular-targeted carriers in blood flow. Specifically, there is a linear relation between particle adhesion and the volume to diameter ratio (VDR) for all the animals, but not for the human model. However there is a significant correlation between particle adhesion density and the ratio of particle diameter to RBC diameter. This suggest that the discrepancies in the particle binding density in different animal models are, in part, due to the different sizes of their RBCs.
Overall, this work elucidates the different trends of particle binding observed in several animal models commonly used in the preclinical research. Our findings addressed many important factors including the effect of RBC size and the type of blood flow that can affect the binding efficiency of vascular-targeted carriers. This study also raises awareness of potential errors that may result from extrapolating in vivo animal model results to human models, which is an important message to many research fields.