A numerical study on drug delivery via multiscale synergy of cellular hitchhiking onto red blood cells.
A numerical study on drug delivery via multiscale synergy of cellular hitchhiking onto red blood cells.
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DOI：
10.1039/d1nr04057j
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发表时间：
2021-09
期刊：
影响因子：
6.7
通讯作者：
M. Nikfar;M. Razizadeh;Ratul Paul;V. Muzykantov;Yaling Liu
中科院分区：
文献类型：
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作者：
M. Nikfar;M. Razizadeh;Ratul Paul;V. Muzykantov;Yaling Liu
红细胞（RBC）搭便车，其中不同的纳米载体（NC）在红细胞膜上穿梭并从RBC解离到静脉注射点下游的第一器官，最近已被引入作为增强靶位点摄取的解决方案。几项实验研究已经证实，细胞搭便车到RBC膜上可以改善小鼠、猪和离体人肺中各种NC的递送。在这些研究中，NC尺寸、NC表面化学和剪切速率对递送过程和生物分布的影响已被广泛探索。为了揭示这种类型的药物输送系统的基础物理，我们提出了一个计算平台的背景下，格子玻尔兹曼方法，弹簧连接网络，摩擦浸没边界方法。所提出的算法模拟纳米粒子（NP）从红细胞表面的剪切流和仿生微流体通道中移出。数值模拟进行了各种NP尺寸和RBC-NP粘附强度。在剪切流中，NP脱离随着剪切速率的增加而增加。红细胞-红细胞相互作用也可以显著促进剪切诱导的颗粒脱离。较大的NP具有更高的从RBC表面断开的倾向。结果表明，改变纳米粒与红细胞之间的相互作用可以控制脱附过程。所有结果与体内和体外实验观察一致。我们相信，所提出的设置可以被利用作为一种预测工具，以估计NP结合的红细胞中的最佳参数，以更好地在组织微血管系统中的靶向程序。
Red blood cell (RBC)-hitchhiking, in which different nanocarriers (NCs) shuttle on the erythrocyte membrane and disassociate from RBCs to the first organ downstream of the intravenous injection spot, has recently been introduced as a solution to enhance target site uptake. Several experimental studies have already approved that cellular hitchhiking onto the RBC membrane can improve the delivery of a wide range of NCs in mice, pigs, and ex vivo human lungs. In these studies, the impact of NC size, NC surface chemistry, and shear rate on the delivery process and biodistribution has been widely explored. To shed light on the underlying physics in this type of drug delivery system, we present a computational platform in the context of the lattice Boltzmann method, spring connected network, and frictional immersed boundary method. The proposed algorithm simulates nanoparticle (NP) dislodgment from the RBC surface in shear flow and biomimetic microfluidic channels. The numerical simulations are performed for various NP sizes and RBC-NP adhesion strengths. In shear flow, NP detachment increases upon increasing the shear rate. RBC-RBC interaction can also significantly boost shear-induced particle detachment. Larger NPs have a higher propensity to be disconnected from the RBC surface. The results illustrate that changing the interaction between the NPs and RBCs can control the desorption process. All the findings agree with in vivo and in vitro experimental observations. We believe that the proposed setup can be exploited as a predictive tool to estimate optimum parameters in NP-bound RBCs for better targeting procedures in tissue microvasculature.