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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。
OBJECTIVE: To establish a physiological-pharmacokinetic model of nanoparticle cell dynamics based on the interaction between nanoparticles and cells. METHODS: Based on the receptor-mediated uptake of NPs, kinetic models describing the uptake and clearance of NPs were established, and the data of cell uptake and clearance of NPs were fitted to obtain the model parameters. Results and experimental data were compared. Results: A kinetic model including nanoparticle compartment and nanoparticle clearance compartment was established, and the numerical calculation method of intracellular nanoparticle content and nanoparticle clearance was obtained. The model parameters were obtained by fitting the cell uptake data and cell clearance data of albumin nanoparticles, and the fitting results of the model were in good agreement with the experimental results. Conclusion: This model can better simulate the kinetics of cell uptake and cell clearance of nanoparticles. Compared with atrioventricular model, the model contains parameters related to cell physiology, so the model has great advantages in the study of nanoparticle multicellular kinetics.