Modeling In Vivo Interactions of Engineered Nanoparticles in the Pulmonary Alveolar Lining Fluid.
Modeling In Vivo Interactions of Engineered Nanoparticles in the Pulmonary Alveolar Lining Fluid.
复制标题
DOI：
10.3390/nano5031223
复制
发表时间：
2015-09
期刊：
影响因子：
--
通讯作者：
Georgopoulos P
中科院分区：
文献类型：
--
作者：
Mukherjee D;Porter A;Ryan M;Schwander S;Chung KF;Tetley T;Zhang J;Georgopoulos P
在消费品中越来越多地使用工程纳米材料（ENM）可能导致广泛的人类吸入暴露。由于其每单位质量的高表面积，吸入的ENM与肺系统的多个组分相互作用，并且这些相互作用影响它们在体内的最终命运。ENM在体内的运输和清除的建模传统上将组织视为良好混合的隔室，而不考虑纳米级的相互作用和转化机制。ENM的聚集、溶解和运输，沿着生物分子如表面活性剂脂质和蛋白质的吸附，导致ENM形态和表面性质的不可逆变化。本文提出的模型量化了肺泡气液界面中ENM的转化和转运，并估计了最终的肺泡细胞剂量学。该配方汇集了胶体和表面科学，物理学和生物化学的既定概念，提供了一个随机的框架，能够捕获肺泡衬里层中的基本体内过程。该模型已实施的体外解决方案的参数估计从相关的体外测量，并已扩展到在体内系统模拟人体吸入暴露。四种不同的ENM的应用程序，并估计相关的动力学速率，证明了一种方法，用于改善人体在体内肺剂量测定。
Increasing use of engineered nanomaterials (ENMs) in consumer products may result in widespread human inhalation exposures. Due to their high surface area per unit mass, inhaled ENMs interact with multiple components of the pulmonary system, and these interactions affect their ultimate fate in the body. Modeling of ENM transport and clearance in vivo has traditionally treated tissues as well-mixed compartments, without consideration of nanoscale interaction and transformation mechanisms. ENM agglomeration, dissolution and transport, along with adsorption of biomolecules, such as surfactant lipids and proteins, cause irreversible changes to ENM morphology and surface properties. The model presented in this article quantifies ENM transformation and transport in the alveolar air to liquid interface and estimates eventual alveolar cell dosimetry. This formulation brings together established concepts from colloidal and surface science, physics, and biochemistry to provide a stochastic framework capable of capturing essential in vivo processes in the pulmonary alveolar lining layer. The model has been implemented for in vitro solutions with parameters estimated from relevant published in vitro measurements and has been extended here to in vivo systems simulating human inhalation exposures. Applications are presented for four different ENMs, and relevant kinetic rates are estimated, demonstrating an approach for improving human in vivo pulmonary dosimetry.