A compartment-quasi-3D multiscale approach for drug absorption, transport, and retention in the human lungs.
A compartment-quasi-3D multiscale approach for drug absorption, transport, and retention in the human lungs.
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DOI：
10.1002/cnm.2955
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发表时间：
2018-05
影响因子：
2.1
通讯作者：
Przekwas A
中科院分区：
文献类型：
--
作者：
Kannan RR;Singh N;Przekwas A
目前用于模拟肺部药物吸收、转运和保留的大多数模型都是 0D 室模型，其中气道通常分为气道和肺泡部分。这种块模型提供低保真度解决方案，并且无法获得空间肺部药物浓度。其他方法利用高保真 CFD 模型，但由于计算成本过高，其能力有限。最近，我们提出了一种新颖、快速运行且稳健的准 3D (Q3D) 模型，用于模拟肺部气流。这种 Q3D 方法保留了 3D 肺部几何形状，提供了极其准确的解决方案，并且速度比 CFD 方法快 25,000 倍。在本文中，我们提出了 Q3D 室多尺度组合来模拟肺部药物吸收、转运和保留。初始沉积是通过 CFD 模拟获得的。 Yu 和 Rosania 的肺吸收室模型适应了这种多尺度格式。肺部以 Q3D 格式建模，直至第 8 代气道。使用隔室对肺部的其余部分以及全身循环和消除过程进行建模。 Q3D 模型进一步适应，允许各种异质环形肺层。这使我们能够模拟跨层和沿肺部的药物转运。使用这种多尺度模型，可以获得不同肺层中的时空药物浓度和血浆中的时间浓度。与标准测试案例的区室模型相比，血浆中的浓度分布与实验结果更加一致。因此，这种多尺度模型可用于优化目标特异性药物输送，增加局部生物利用度，从而促进从实验室到临床的各种患者/肺部疾病变化的应用。
The majority of current models used for modeling the pulmonary drug absorption, transport, and retention are 0D compartmental models where the airways are generally split into the airways and alveolar sections. Such block models deliver low fidelity solutions and the spatial lung drug concentrations cannot be obtained. Other approaches utilize high fidelity CFD models with limited capabilities due to their exorbitant computational cost. Recently, we presented a novel, fast-running and robust Quasi-3D (Q3D) model for modeling the pulmonary airflow. This Q3D method preserved the 3D lung geometry, delivered extremely accurate solutions and was 25,000 times faster in comparison to the CFD methods. In this paper, we present a Q3D-compartment multiscale combination to model the pulmonary drug absorption, transport, and retention. The initial deposition is obtained from CFD simulations. The lung absorption compartment model of Yu and Rosania is adapted to this multiscale format. The lung is modeled in the Q3D format till 8th airway generation. The remainder of the lung along with the systemic circulation and elimination processes were modeled using compartments. The Q3D model is further adapted, by allowing for various heterogeneous annular lung layers. This allows us to model the drug transport across the layers and along the lung. Using this multiscale model, the spatio-temporal drug concentrations in the different lung layers and the temporal concentration in the plasma are obtained. The concentration profile in the plasma was found to be better aligned with the experimental findings in comparison with compartmental model for the standard test cases. Thus, this multiscale model can be used to optimize the target-specific drug delivery, increase the localized bio-availability, thereby facilitating applications from the bench to bedside for various patient/lung-disease variations.
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影响因子：
3.8
作者：
Choi, Jiwoong;Xia, Guohua;Tawhai, Merryn H.;Hoffman, Eric A.;Lin, Ching-Long
通讯作者：
Lin, Ching-Long
影响因子：
56.9
作者：
Edwards, DA;Hanes, J;Langer, R
通讯作者：
Langer, R
影响因子：
6.7
作者：
Raaska, K;Niemi, M;Kivistö, KT
通讯作者：
Kivistö, KT
DOI：
10.1002/cnm.2838
发表时间：
2017-07-01
影响因子：
2.1
作者：
Kannan, Ravishekar;Chen, Z. J.;Walenga, Ross
通讯作者：
Walenga, Ross
影响因子：
5.8
作者：
Paixao, Paulo;Gouveia, Luis F.;Morais, Jose A. G.
通讯作者：
Morais, Jose A. G.