Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
Biomaterials. 2010 Feb;31(6):1392-402. doi: 10.1016/j.biomaterials.2009.11.007. Epub 2009 Dec 2.
Targeting of drug carriers to the vascular wall is of interest for localized delivery of therapeutics in many human diseases. Nanometer-sized spherical particles are widely proposed for use as carriers for vascular targeting, yet very little evidence has been presented as to their ability to interact with the vascular wall. Thus, this work focuses on elucidating the effect of particle size along with hemodynamics, blood rheology, and vessel size on the adhesion efficiency of targeted polymeric spheres to inflamed endothelium in vitro via parallel plate flow chamber assays. We find that the binding efficiency of spheres to the endothelium from blood flow generally increased with increasing particle size, wall shear rate and channel height for particle sizes from 100 nm up to 10 microm. However, nano-sized particles showed minimal adhesion to the endothelium from blood flow in horizontal (gravity or anti-gravity direction) and vertical channels on the order of small to medium-sized venules and arteries when compared to micron-sized spheres. Furthermore, adhesion of nanospheres was not enhanced with pulsatility in flow. Overall, the presented data suggests that spheres 2-5 microm in size are optimal for targeting the wall in medium to large vessels relevant in several cardiovascular diseases.
靶向药物载体到血管壁是为了在许多人类疾病中实现治疗药物的局部递送。纳米级球形颗粒被广泛提议用作血管靶向载体，但很少有证据表明它们能够与血管壁相互作用。因此，这项工作侧重于通过平行板流动腔测定体外阐明颗粒大小以及血液动力学、血液流变学和血管大小对靶向聚合物球体与炎症内皮黏附效率的影响。我们发现，从血流中，球体与内皮的结合效率通常随颗粒尺寸的增加而增加，对于从 100nm 到 10μm 的颗粒尺寸，壁剪切率和通道高度也随之增加。然而，与微米级球体相比，纳米级颗粒在水平（重力或反重力方向）和垂直通道中从血流到中小静脉和动脉的内皮的黏附性最小。此外，流动中的脉动并没有增强纳米球的黏附性。总的来说，所呈现的数据表明，对于靶向几种心血管疾病中相关的中等至大血管的壁，大小为 2-5μm 的球体是最佳选择。
