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粒径和形状对其边缘和壁附着的影响:对纳米到微米尺度药物输送载体设计的影响。

Influence of particle size and shape on their margination and wall-adhesion: implications in drug delivery vehicle design across nano-to-micro scale.

机构信息

Case Western Reserve University, Department of Biomedical Engineering, Cleveland, Ohio, USA.

出版信息

Nanoscale. 2018 Aug 16;10(32):15350-15364. doi: 10.1039/c8nr04042g.


DOI:10.1039/c8nr04042g
PMID:30080212
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6247903/
Abstract

Intravascular drug delivery technologies majorly utilize spherical nanoparticles as carrier vehicles. Their targets are often at the blood vessel wall or in the tissue beyond the wall, such that vehicle localization towards the wall (margination) becomes a pre-requisite for their function. To this end, some studies have indicated that under flow environment, micro-particles have a higher propensity than nano-particles to marginate to the wall. Also, non-spherical particles theoretically have a higher area of surface-adhesive interactions than spherical particles. However, detailed systematic studies that integrate various particle size and shape parameters across nano-to-micro scale to explore their wall-localization behavior in RBC-rich blood flow, have not been reported. We address this gap by carrying out computational and experimental studies utilizing particles of four distinct shapes (spherical, oblate, prolate, rod) spanning nano- to-micro scale sizes. Computational studies were performed using the Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) package, with Dissipative Particle Dynamics (DPD). For experimental studies, model particles were made from neutrally buoyant fluorescent polystyrene spheres, that were thermo-stretched into non-spherical shapes and all particles were surface-coated with biotin. Using microfluidic setup, the biotin-coated particles were flowed over avidin-coated surfaces in absence versus presence of RBCs, and particle adhesion and retention at the surface was assessed by inverted fluorescence microscopy. Our computational and experimental studies provide a simultaneous analysis of different particle sizes and shapes for their retention in blood flow and indicate that in presence of RBCs, micro-scale non-spherical particles undergo enhanced 'margination + adhesion' compared to nano-scale spherical particles, resulting in their higher binding. These results provide important insight regarding improved design of vascularly targeted drug delivery systems.

摘要

血管内药物输送技术主要利用球形纳米颗粒作为载体。它们的目标通常是在血管壁或壁外的组织中,因此载体向壁的定位(边缘定位)成为其功能的前提。为此,一些研究表明,在流动环境下,微颗粒比纳米颗粒更有可能向壁边缘定位。此外,非球形颗粒理论上比球形颗粒具有更高的表面积粘附相互作用面积。然而,尚未有报道详细系统地研究跨越纳至微尺度的各种颗粒尺寸和形状参数,以探索它们在富含红细胞的血流中的壁定位行为。我们通过利用四种不同形状(球形、扁球形、长球形、棒形)的颗粒进行计算和实验研究来解决这一差距,这些颗粒跨越纳至微尺度尺寸。计算研究使用了大规模原子/分子大规模并行模拟器(LAMMPS)包和耗散粒子动力学(DPD)进行。对于实验研究,模型颗粒由中性浮力荧光聚苯乙烯球制成,这些球被热拉伸成非球形形状,所有颗粒都表面涂有生物素。使用微流控装置,将生物素涂层的颗粒在缺乏和存在红细胞的情况下流过亲和素涂层的表面,并通过倒置荧光显微镜评估颗粒在表面的粘附和保留情况。我们的计算和实验研究提供了对不同颗粒尺寸和形状的保留进行同时分析的方法,表明在存在红细胞的情况下,与纳米级球形颗粒相比,微尺度非球形颗粒经历了增强的“边缘定位+粘附”,从而导致其更高的结合。这些结果为血管靶向药物输送系统的改进设计提供了重要的见解。

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本文引用的文献

[1]
Flexible Nanoparticles Reach Sterically Obscured Endothelial Targets Inaccessible to Rigid Nanoparticles.

Adv Mater. 2018-6-28

[2]
Presence of Rigid Red Blood Cells in Blood Flow Interferes with the Vascular Wall Adhesion of Leukocytes.

Langmuir. 2018-1-31

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Sci Rep. 2017-11-10

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Margination and stretching of von Willebrand factor in the blood stream enable adhesion.

Sci Rep. 2017-10-27

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Nat Nanotechnol. 2017-4-10

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