title: Effect of variation in hemorheology between human and animal blood on the binding efficacy of vascular-targeted carriers.
abstract: Animal models are extensively used to evaluate the in vivo functionality of novel drug delivery systems (DDS). However, many variations likely exist in vivo between the animals and human physiological environment that significantly alter results obtained with animal models relative to human system. To date, it is not clear if the variation in hemorheology and hemodynamics between common animal and human models affect the functionality of DDS. This study investigates the role of hemorheology of humans and various animal models in dictating the binding efficiency of model vascular-targeted carriers (VTCs) to the wall in physiological blood flows. Specifically, the adhesion of sLe(A)-coated nano- and micro-spheres to inflamed endothelial cells monolayers were conducted via a parallel plate flow chamber assay with steady and disturbed red blood cells (RBCs)-in-buffer and whole blood flows of common animal models. Our results suggest that the ratio of carrier size to RBC size dictate particle binding in blood flow. Additionally, the presence of white blood cells affects the trend of particle adhesion depending on the animal species. Overall, this work sheds light on some deviation in VTC vascular wall interaction results obtained with in vivo animal experimentation from expected outcome and efficiency in vivo in human.
authors.affiliation: Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109.
authors.forename: K
authors.initials: K
authors.lastname: Namdee
authors.affiliation: Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109.
authors.forename: M
authors.initials: M
authors.lastname: Carrasco-Teja
authors.affiliation: Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109.
authors.forename: M B
authors.initials: MB
authors.lastname: Fish
authors.affiliation: Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109.
authors.forename: P
authors.initials: P
authors.lastname: Charoenphol
authors.affiliation: Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109.
authors.forename: O
authors.initials: O
authors.lastname: Eniola-Adefeso
mesh_terms: D000328:Adult; D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology; D002448:Cell Adhesion; D048429:Cell Size; D002478:Cells, Cultured; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D004912:Erythrocytes / Q000378:metabolism*; D006439:Hemodynamics / Q000502:physiology*; D018056:Hemorheology / Q000502:physiology*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D008863:Microspheres; D009010:Monte Carlo Method; D054118:Nanospheres / Q000737:chemistry; D010316:Particle Size; D011817:Rabbits; D013045:Species Specificity; D013552:Swine
chemical_list: D004337:Drug Carriers