Influence of Red Blood Cells on Nanoparticle Targeted Delivery in Microcirculation.
Influence of Red Blood Cells on Nanoparticle Targeted Delivery in Microcirculation.
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DOI：
10.1039/c2sm06391c
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发表时间：
2011-12-22
期刊：
影响因子：
3.4
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Tan J;Thomas A;Liu Y
多功能纳米医学作为下一代药物具有相当大的前景，它允许以最小的毒性进行靶向治疗。目前大多数关于纳米颗粒（NP）药物递送的研究都考虑悬浮纳米颗粒的牛顿流体。然而，血液是一种复杂的生物液体，由可变形的细胞、蛋白质、血小板和血浆组成。对于毛细血管、小动脉和小静脉的血液流动，在输送过程中需要考虑血液的颗粒性。细胞自由层和np -细胞相互作用的存在将在很大程度上影响分散率和结合率，从而影响靶向递送效率。本文建立了一个粒子-细胞混合模型来模拟NP在血液悬浮液中的运输、分散和结合动力学。通过浸入式有限元法捕获红细胞的运动和变形。通过布朗黏附动力学来跟踪单个NPs的运动和粘附。引入映射算法和相互作用势函数来考虑细胞-粒子碰撞。根据所建立的模型，在不同的流变条件下得到了NP的分散和结合率。研究了红细胞、血管流速和颗粒大小对NP分布和递送效果的影响。在血管壁附近观察到颗粒浓度较高的非均匀NP分布。与不考虑红细胞的情况相比，这种分布导致颗粒结合率高出50%以上。红细胞在毛细管核心区域的翻滚运动增强了NP弥散，随着剪切速率的增加，弥散速率也随之增加。本研究的结果有助于对血液颗粒性质如何影响NP递送的基本理解和认识，这将为靶向药物递送应用的纳米医学设计提供机制见解。
Multifunctional nanomedicine holds considerable promise as the next generation of medicine that allows for targeted therapy with minimal toxicity. Most current studies on Nanoparticle (NP) drug delivery consider a Newtonian fluid with suspending NPs. However, blood is a complex biological fluid composed of deformable cells, proteins, platelets, and plasma. For blood flow in capillaries, arterioles and venules, the particulate nature of the blood needs to be considered in the delivery process. The existence of the cell-free-layer and NP-cell interaction will largely influence both the dispersion and binding rates, thus impact targeted delivery efficacy. In this paper, a particle-cell hybrid model is developed to model NP transport, dispersion, and binding dynamics in blood suspension. The motion and deformation of red blood cells is captured through the Immersed Finite Element Method. The motion and adhesion of individual NPs are tracked through Brownian adhesion dynamics. A mapping algorithm and an interaction potential function are introduced to consider the cell-particle collision. NP dispersion and binding rates are derived from the developed model under various rheology conditions. The influence of red blood cells, vascular flow rate, and particle size on NP distribution and delivery efficacy is characterized. A non-uniform NP distribution profile with higher particle concentration near the vessel wall is observed. Such distribution leads to over 50% higher particle binding rate compared to the case without RBC considered. The tumbling motion of RBCs in the core region of the capillary is found to enhance NP dispersion, with dispersion rate increases as shear rate increases. Results from this study contribute to the fundamental understanding and knowledge on how the particulate nature of blood influences NP delivery, which will provide mechanistic insights on the nanomedicine design for targeted drug delivery applications.