Department of Chemical Engineering, University of Michigan, 2300 Hayward Street, 3074 H. H. Dow Building, Ann Arbor, MI 48109, USA.
J Biomech. 2012 Nov 15;45(16):2822-8. doi: 10.1016/j.jbiomech.2012.08.035. Epub 2012 Sep 23.
The outcome of vascular-targeted therapies is generally determined by how efficiently vascular-targeted carriers localize and adhere to the endothelial wall at the targeted site. This study investigates the impact of leukocytes, platelets and red blood cells on the margination of vascular-targeted polymeric nanospheres and microspheres under various physiological blood flow conditions. We report that red blood cells either promote or hinder particle adhesion to an endothelial wall in a parallel plate flow chamber depending on the blood flow pattern, hematocrit, and particle size. Leukocytes prevent microspheres - but not nanospheres - from adhering in laminar and pulsatile flows via (1) competition for the available binding space and (2) physical removal of previously bound spheres. In recirculating blood flow, the negative effect of leukocytes on particle adhesion is minimal for large microspheres in the disturbed flow region beyond the flow reattachment. Resting platelets were found to have no effect on particle binding likely due to their dimensions and minimal interaction with the endothelial wall. Overall, the findings of the present work would be critical for designing effective vascular-targeted carriers for imaging and drug delivery applications in several human diseases.
血管靶向治疗的效果通常取决于血管靶向载体在靶向部位与内皮壁的定位和黏附效率。本研究旨在探讨白细胞、血小板和红细胞对不同生理血流条件下血管靶向聚合物纳米球和微球边缘形成的影响。我们的研究结果表明，红细胞会根据血流模式、红细胞压积和粒径的不同，促进或阻碍粒子在平板流动腔中黏附于内皮壁。白细胞通过（1）争夺可用的结合空间和（2）物理去除已结合的球体，防止微球——而非纳米球——在层流和脉动流中黏附。在再循环血流中，对于再附着点之后的紊乱流区中的大微球，白细胞对粒子黏附的负面影响最小。静止的血小板由于其尺寸和与内皮壁的最小相互作用，被发现对粒子结合没有影响。总的来说，本研究结果对于设计用于几种人类疾病的成像和药物输送的有效血管靶向载体至关重要。
