Institute of Bio-Economy and Agri-Technology, Centre for Research and Technology Hellas (CERTH), 38333 Volos, Greece.
Institute of Bio-Economy and Agri-Technology, Centre for Research and Technology Hellas (CERTH), 38333 Volos, Greece.
Comput Methods Programs Biomed. 2021 Nov;212:106477. doi: 10.1016/j.cmpb.2021.106477. Epub 2021 Oct 19.
Glioblastoma multiforme is considered as one of the most aggressive types of cancer, while various treatment techniques have been proposed. Magnetic nanoparticles (MNPs) loaded with drug and magnetically controlled and targeted to tissues affected by disease, is considered as a possible treatment. However, MNPs are difficult to penetrate the central nervous system and approach the unhealthy tissue, because of the blood-brain barrier (BBB). This study investigates numerically the delivery of magnetic nanoparticles through the barrier driven by normal pressure drop and external gradient magnetic fields, employing a simplified geometrical model, computational fluid dynamics and discrete element method. The goal of the study is to provide information regarding the permeability of the BBB under various conditions like the imposed forces and the shape of the domain, as a preliminary predictive tool.
To achieve that, the three-dimensional Navier-Stokes equations are solved in the margin of a blood vessel along with a discrete model for the MNPs with various acting forces. The numerical results are compared with experimental measurements showing that the model can predict acceptably the flow behavior.
The effect of nanoparticles' size, external magnetic field and blood flow in the vessel, on the brain-barrier's permeability are investigated. Three different cases of available area among the endothelial cells per the MNPs' size ratio are also examined, showing that the MNPs' size and available area is not the dominant parameter affecting the permeability of the BBB. The results indicate that the applied magnetic field enhances the drug delivery into the central nervous system (CNS). When larger MNPs (∼100 nm) are exposed to an external magnetic field, the permeability can be improved up to 30%, while it is shown that smaller MNPs (∼10 nm) cannot be driven by the applied magnetic field and in this case the permeability remains relatively unchanged. Finally, the blood flow increase leads to a permeability improvement up to 15%.
The applied magnetic field improves up to 45% the permeability of the BBB for MNPs of 100 nm. The geometric characteristics of the endothelial cells, the nanoparticles' size and the blood flow are not so decisive parameters for the drug delivery into the CNS, compared to the external magnetic force.
多形性胶质母细胞瘤被认为是最具侵袭性的癌症之一，目前已经提出了各种治疗技术。载药磁性纳米颗粒（MNPs）可以在外加磁场的控制下靶向病变组织，这被认为是一种有前途的治疗方法。然而，由于血脑屏障（BBB）的存在，MNPs 很难穿透中枢神经系统并到达不健康的组织。本研究通过数值模拟的方法，利用简化的几何模型、计算流体力学和离散元方法，研究了在外加压力降和外部梯度磁场作用下 MNPs 通过血脑屏障的传递过程。该研究的目的是提供不同条件下（如施加的力和域的形状）BBB 通透性的信息，作为初步的预测工具。
为了实现这一目标，在血管边缘处求解了三维纳维-斯托克斯方程，并采用了带有各种作用力的 MNPs 离散模型。数值结果与实验测量结果进行了比较，结果表明该模型可以很好地预测流动行为。
研究了纳米颗粒的大小、外加磁场和血管内血流对血脑屏障通透性的影响。还研究了 MNPs 大小与内皮细胞之间的可用面积的三种不同情况，结果表明 MNPs 的大小和可用面积不是影响 BBB 通透性的主导参数。结果表明，施加的磁场可以增强药物向中枢神经系统（CNS）的传递。当较大的 MNPs（∼100nm）暴露于外加磁场时，通透性可以提高 30%，而较小的 MNPs（∼10nm）则不能被外加磁场驱动，在这种情况下，通透性保持相对不变。最后，血流增加导致通透性提高了 15%。
对于 100nm 的 MNPs，外加磁场可以将 BBB 的通透性提高 45%。与外加磁场相比，内皮细胞的几何特征、纳米颗粒的大小和血流对药物向 CNS 的传递不是决定性因素。
