Effect of variation in hemorheology between human and animal blood on the binding efficacy of vascular-targeted carriers.

Effect of variation in hemorheology between human and animal blood on the binding efficacy of vascular-targeted carriers.
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人与动物血液之间血液学变异对血管靶向载体的结合功效的影响。

DOI:
10.1038/srep11631
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发表时间:
2015-06-26
期刊:
影响因子:
4.6
通讯作者:
Eniola-Adefeso O
Eniola-Adefeso O
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Namdee K;Carrasco-Teja M;Fish MB;Charoenphol P;Eniola-Adefeso O

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动物模型广泛用于评估新型药物递送系统(DDS)的体内功能。然而,动物体内和人类生理环境之间可能存在许多差异,这些差异显着改变了动物模型相对于人类系统获得的结果。迄今为止,尚不清楚常见动物和人类模型之间血液流变学和血流动力学的差异是否会影响 DDS 的功能。本研究调查了人类和各种动物模型的血液流变学在决定模型血管靶向载体 (VTC) 与生理血流中壁的结合效率方面的作用。具体而言,通过平行板流室测定,对缓冲液中稳定和受干扰的红细胞 (RBC) 以及常见动物模型的全血流进行了 sLeA 涂层纳米球和微球与发炎内皮细胞单层的粘附。我们的结果表明,载体尺寸与红细胞尺寸的比率决定了血流中的颗粒结合。此外,白细胞的存在会影响颗粒粘附的趋势,具体取决于动物种类。总体而言,这项工作揭示了体内动物实验获得的 VTC 血管壁相互作用结果与人类体内预期结果和效率的一些偏差。
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 sLeA-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.
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