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Influence of particle size and shape on their margination and wall-adhesion: implications in drug delivery vehicle design across nano-to-micro scale†
Nanoscale ( IF 5.8 ) Pub Date : 2018-08-01 00:00:00 , DOI: 10.1039/c8nr04042g Michaela Cooley 1 , Apoorva Sarode , Masoud Hoore , Dmitry A Fedosov , Samir Mitragotri , Anirban Sen Gupta
Nanoscale ( IF 5.8 ) Pub Date : 2018-08-01 00:00:00 , DOI: 10.1039/c8nr04042g Michaela Cooley 1 , Apoorva Sarode , Masoud Hoore , Dmitry A Fedosov , Samir Mitragotri , Anirban Sen Gupta
Affiliation
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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.
中文翻译：
颗粒尺寸和形状对其边缘和壁粘附的影响：对纳米到微米尺度药物输送载体设计的影响†
血管内药物递送技术主要利用球形纳米粒子作为载体。它们的目标通常位于血管壁或血管壁以外的组织中，因此车辆朝向血管壁的定位（边缘化）成为其功能的先决条件。为此，有研究表明，在流动环境下，微米颗粒比纳米颗粒更容易边缘化于壁面。此外，理论上非球形颗粒比球形颗粒具有更大的表面粘附相互作用面积。然而，整合纳米到微米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的详细系统研究尚未报道。我们通过利用跨越纳米到微米尺度的四种不同形状（球形、扁圆形、扁长形、棒形）的颗粒进行计算和实验研究来解决这一差距。使用大规模原子/分子大规模并行模拟器 (LAMMPS) 包和耗散粒子动力学 (DPD) 进行计算研究。在实验研究中，模型颗粒由中性浮力荧光聚苯乙烯球制成，热拉伸成非球形，所有颗粒表面均涂有生物素。使用微流体装置，在不存在红细胞的情况下与存在红细胞的情况下，生物素包被的颗粒流过抗生物素蛋白包被的表面，并通过倒置荧光显微镜评估颗粒在表面的粘附和保留。我们的计算和实验研究同时分析了不同粒径和形状的颗粒在血流中的滞留情况，并表明在存在红细胞的情况下，与纳米级球形颗粒相比，微米级非球形颗粒的“边缘化+粘附”增强，导致它们的结合力更高。这些结果为改进血管靶向药物输送系统的设计提供了重要的见解。
更新日期：2018-08-01
中文翻译：
颗粒尺寸和形状对其边缘和壁粘附的影响：对纳米到微米尺度药物输送载体设计的影响†
血管内药物递送技术主要利用球形纳米粒子作为载体。它们的目标通常位于血管壁或血管壁以外的组织中，因此车辆朝向血管壁的定位（边缘化）成为其功能的先决条件。为此，有研究表明，在流动环境下，微米颗粒比纳米颗粒更容易边缘化于壁面。此外，理论上非球形颗粒比球形颗粒具有更大的表面粘附相互作用面积。然而，整合纳米到微米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的详细系统研究尚未报道。我们通过利用跨越纳米到微米尺度的四种不同形状（球形、扁圆形、扁长形、棒形）的颗粒进行计算和实验研究来解决这一差距。使用大规模原子/分子大规模并行模拟器 (LAMMPS) 包和耗散粒子动力学 (DPD) 进行计算研究。在实验研究中，模型颗粒由中性浮力荧光聚苯乙烯球制成，热拉伸成非球形，所有颗粒表面均涂有生物素。使用微流体装置，在不存在红细胞的情况下与存在红细胞的情况下，生物素包被的颗粒流过抗生物素蛋白包被的表面，并通过倒置荧光显微镜评估颗粒在表面的粘附和保留。我们的计算和实验研究同时分析了不同粒径和形状的颗粒在血流中的滞留情况，并表明在存在红细胞的情况下，与纳米级球形颗粒相比，微米级非球形颗粒的“边缘化+粘附”增强，导致它们的结合力更高。这些结果为改进血管靶向药物输送系统的设计提供了重要的见解。
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