一种纳米粒细胞动力学的生理药动学模型的建立与解析

目的：以纳米粒与细胞的相互作用过程为基础，建立一种纳米粒细胞动力学的生理药动学模型。方法：以受体介导的纳米粒细胞摄取过程为基础，建立描述纳米粒细胞摄取和细胞清除的动力学模型，对纳米粒的细胞摄取和清除数据进行拟合，获取模型参数，并将拟合结果与实验数据进行对比。结果：建立了一种包含纳米粒隔室和纳米粒清除隔室的动力学模型，并且获得了细胞内纳米粒含量和纳米粒消除量的数值计算方法。通过对白蛋白纳米粒的细胞摄取数据和细胞清除数据的拟合，获取了模型参数，并且模型的拟合结果与实验测定结果相符。结论：该模型能较好地对纳米粒的细胞摄取-细胞清除的动力学进行模拟。同房室模型相比，该模型含有与细胞生理因素有关的模型参数，因此该模型在对纳米粒多细胞动力学研究中具有较大的优势。

Establishment and analysis of a physiologically based pharmacokinetic model for intracellular kinetics of nanoparticles

OBJECTIVE To establish a physiologically based pharmacokinetic model for intracellular kinetics of nanoparticles (NPs) basing on interaction process of nanoparticles and cells.METHODS Based on receptor mediated cellular uptake of NPs, a model describing intracellular uptake and clearance of NPs was developed, and experimental results were fitted using this model to obtain relevant parameters. Kinetic process calculated by using this model was compared with results obtained from the experiment.RESULTS A kinetic model containing NPs compartment and NPs' clearance compartment was developed, and calculation method was established for intracellular NPs amount and the clearance of NPs. By fitting intracellular NPs amount and clearance of NPs determined by the experiment, parameters of model were obtained, and kinetic process calculated by model agreed well with experimental results.CONCLUSION Intracellular uptake and clearance of NPs can fit well with model developed in this study. Compared with compartment model, this model contains a parameter related with physiological factors of cells. Therefore, this model has greater advantages for studies related with kinetics of NPs in different kinds of cells.