Ye Huilin, Shen Zhiqiang, Yu Le, Wei Mei, Li Ying
Department of Mechanical Engineering, University of Connecticut, 191 Auditorium Road, Unit 3139, Storrs, Connecticut 06269, United States.
Department of Materials Science and Engineering, University of Connecticut, 97 North Eagleville Road, Unit 3136, Storrs, Connecticut 06269, United States.
ACS Biomater Sci Eng. 2018 Jan 8;4(1):66-77. doi: 10.1021/acsbiomaterials.7b00434. Epub 2017 Dec 5.
Nanomaterials have been widely used in the design of drug delivery platforms. This work computationally explores the vascular dynamics of nanoworms as drug carriers within blood flow by considering the effects of nanoworm length, stiffness, and local physiological conditions such as hematocrit. We found that nanoworms with length of 8 μm and moderate stiffness are the optimal choice as drug carriers for circulating within normal vascular network due to their lower near wall margination. Compared to those of spherical rigid particles, these nanoworms demonstrate significant demargination behaviors at hematocrit 20%, induced by the local hydrodynamic interactions. Specifically, the interactions between nanoworms and red blood cells create asymmetrical local flow fields, resulting in the demargination of nanoworms. In addition, the flexibility of nanoworms enables them to conform to the deformed shape of red blood cells under shear flow, leading to their high concentration within the core region of vessels. Therefore, the long blood circulation time of nanoworms can be partially attributed to their demargination behaviors and intertwinement with red blood cells. According to these simulation results, tuning the length and stiffness of nanoworms is the key to design drug carries with reduced near wall margination within normal vascular networks and extend their blood circulation time.
纳米材料已广泛应用于药物递送平台的设计。本研究通过考虑纳米蠕虫的长度、刚度以及诸如血细胞比容等局部生理条件,对纳米蠕虫作为血流中药物载体的血管动力学进行了计算探索。我们发现,长度为8μm且具有适度刚度的纳米蠕虫是在正常血管网络中循环的最佳药物载体选择,因为它们的近壁边缘化程度较低。与球形刚性颗粒相比,这些纳米蠕虫在血细胞比容为20%时表现出显著的去边缘化行为,这是由局部流体动力学相互作用引起的。具体而言,纳米蠕虫与红细胞之间的相互作用产生不对称的局部流场,导致纳米蠕虫的去边缘化。此外,纳米蠕虫的柔韧性使它们能够在剪切流下顺应红细胞的变形形状,从而在血管核心区域内实现高浓度分布。因此,纳米蠕虫较长的血液循环时间可部分归因于它们的去边缘化行为以及与红细胞的缠绕。根据这些模拟结果,调整纳米蠕虫的长度和刚度是设计在正常血管网络中具有降低的近壁边缘化且延长其血液循环时间的药物载体的关键。