Additional file 1 of Development of a multi-route physiologically based pharmacokinetic (PBPK) model for nanomaterials: a comparison between a traditional versus a new route-specific approach using gold nanoparticles in rats
Creators: name: Chou, Wei-Chun
name: Cheng, Yi-Hsien
name: Riviere, Jim E.
name: Monteiro-Riviere, Nancy A.
name: Kreyling, Wolfgang G.
name: Lin, Zhoumeng
Publisher: name: figshare
Year: 2022
Subjects: subject: Biotechnology
subject: Ecology
subject: FOS: Biological sciences
subject: 69999 Biological Sciences not elsewhere classified
subject: 80699 Information Systems not elsewhere classified
subject: FOS: Computer and information sciences
subject: 19999 Mathematical Sciences not elsewhere classified
subject: FOS: Mathematics
subject: Cancer

description: Additional file 1. Section 1: Equations and codes for the multiple-route AuNPs PBPK model. Section 2: Methods on preliminary model calibration. Section 3: Methods on estimation of posterior parameter within Bayesian framework. Section 4: Model calibration results. Section 5. Sensitivity analysis methods. Table S1: Physicochemical characteristics of gold nanoparticles and dosing information of pharmacokinetic studies used in the PBPK model. Table S2: Physiological parameters used in the multi-route PBPK model for gold nanoparticles in rats. Table S3: Gold nanoparticle-specific parameters used in the PBPK model after various routes of administration in rats. Table S4: Posterior uncertainty distributions for the population mean (µ) and variance ( $${\Sigma }^{2}$$ Σ 2 ) of the PBPK model parameters following oral administration. Table S5: Posterior uncertainty distributions for the population mean (µ) and variance ( $${\Sigma }^{2}$$ Σ 2 ) of the PBPK model parameters following intravenous administration. Table S6: Posterior uncertainty distributions for the population mean (µ) and variance ( $${\Sigma }^{2}$$ Σ 2 ) of the PBPK model parameters following intratracheal instillation. Table S7: Posterior uncertainty distributions for the population mean (µ) and variance ( $${\Sigma }^{2}$$ Σ 2 ) of the PBPK model parameters following endotracheal inhalation for 23 nm AuNPs. Table S8: Normalized sensitivity coefficients (NSCs) of highly influential parameters after oral administration to 5 nm AuNPs. Table S9: Normalized sensitivity coefficients (NSCs) of highly influential parameters after intravenous (IV) administration to 5 nm AuNPs. Table S10: Normalized sensitivity coefficients (NSCs) of highly influential parameters after intratracheal instillation to 5 nm AuNPs. Table S11: Normalized sensitivity coefficients (NSCs) of highly influential parameters after inhalation administration to 23 nm AuNPs. Table S12: Final multivariate linear regression models describing relationships between the physicochemical properties of AuNPs and biodistribution parameters following oral gavage. Table S13: Final multivariate linear regression models describing relationships between the physicochemical properties of AuNPs and biodistribution parameters following intratracheal instillation. Table S14: Main physicochemical characteristics of the AuNPs in the selected pharmacokinetic studies used for model evaluation in this study. Table S15: Model-predicted and measured amount of AuNPs in blood, GI, Kidneys, Liver, Lungs and spleen. Figure S1: Schematic diagram of the multi-route physiologically based pharmacokinetic (PBPK) model for 1.4, 5, 18, 23, 80, and 200 nm gold nanoparticles (AuNPs) in adult rats. Figure S2: PBPK model simulation results compared with 24-h IV-based pharmacokinetic data of 1.4, 5, 18, 80, and 200 nm AuNPs in healthy rats. Figure S3: PBPK model simulation results compared with 24-h pharmacokinetic data of 5, 18, 80, and 200 nm AuNPs in rats following oral gavage. Figure S4: PBPK model simulation results compared with 24-h pharmacokinetic data of 5, 18, 80, and 200 nm AuNPs in rats following oral gavage. Figure S5: PBPK model calibration with 28-d pharmacokinetic data in rats after inhalation of 23 nm aerosolized AuNPs via endotracheal tube for 2 h. Figure S6: PBPK model calibration results with pharmacokinetic data of 1.4, 5, 18, 80 and 200 nm AuNPs in rats after intravenous injection. Figure S7: PBPK model calibration results with pharmacokinetic data of 5, 18, 80 and 200 nm AuNPs in rats after oral administration. Figure S8: PBPK model calibration results with pharmacokinetic data of 1.4, 5, 18, 80 and 200 nm AuNPs in rats after intratracheal instillation. Figure S9: Heat map plot of the normalized sensitivity coefficient (NSC) for comparative sensitivity analyses for 18, 80 and 200 nm AuNPs at 24 h and 672 h following oral administration, IV injection, and IT instillation. Figure S10: Comparisons of model prediction (x-axis) with observed data (y-axis) for the validation datasets. Section 8: Tutorial for Nano-iPBPK interface. Section 9: Supplementary references.