skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: ISD3: a particokinetic model for predicting the combined effects of particle sedimentation, diffusion and dissolution on cellular dosimetry for in vitro systems

Abstract

The development of particokinetic models describing the delivery of insoluble or poorly soluble nanoparticles to cells in liquid cell culture systems has improved the basis for dose-response analysis, hazard ranking from high-throughput systems, and now allows for translation of exposures across in vitro and in vivo test systems. Complimentary particokinetic models that address processes controlling delivery of both particles and released ions to cells, and the influence of particle size changes from dissolution on particle delivery for cell-culture systems would help advance our understanding of the role of particles ion dosimetry on cellular toxicology. We developed ISD3, an extension of our previously published model for insoluble particles, by deriving a specific formulation of the Population Balance Equation for soluble particles. ISD3 describes the time, concentration and particle size dependent dissolution of particles, their delivery to cells, and the delivery and uptake of ions to cells in in vitro liquid test systems. The model is modular, and can be adapted by application of any empirical model of dissolution, alternative approaches to calculating sedimentation rates, and cellular uptake or treatment of boundary conditions. We apply the model to calculate the particle and ion dosimetry of nanosilver and silver ions in vitro aftermore » calibration of two empirical models, one for particle dissolution and one for ion uptake. The results demonstrate utility and accuracy of the ISD3 framework for dosimetry in these systems. Total media ion concentration, particle concentration and total cell-associated silver time-courses were well described by the model, across 2 concentrations of 20 and 110 nm particles. ISD3 was calibrated to dissolution data for 20 nm particles as a function of serum protein concentration, but successfully described the media and cell dosimetry time-course for both particles at all concentrations and time points. We also report the finding that protein content in media has effects both on the initial rate of dissolution and the resulting near-steady state ion concentration in solution.« less

Authors:
; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1439688
Report Number(s):
PNNL-SA-125563
Journal ID: ISSN 1743-8977; 400412000
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Particle and Fibre Toxicology; Journal Volume: 15; Journal Issue: 1
Country of Publication:
United States
Language:
English
Subject:
silver nanoparticle; dosimetry; population balance; silver dissolution

Citation Formats

Thomas, Dennis G., Smith, Jordan N., Thrall, Brian D., Baer, Donald R., Jolley, Hadley, Munusamy, Prabhakaran, Kodali, Vamsi, Demokritou, Philip, Cohen, Joel, and Teeguarden, Justin G. ISD3: a particokinetic model for predicting the combined effects of particle sedimentation, diffusion and dissolution on cellular dosimetry for in vitro systems. United States: N. p., 2018. Web. doi:10.1186/s12989-018-0243-7.
Thomas, Dennis G., Smith, Jordan N., Thrall, Brian D., Baer, Donald R., Jolley, Hadley, Munusamy, Prabhakaran, Kodali, Vamsi, Demokritou, Philip, Cohen, Joel, & Teeguarden, Justin G. ISD3: a particokinetic model for predicting the combined effects of particle sedimentation, diffusion and dissolution on cellular dosimetry for in vitro systems. United States. doi:10.1186/s12989-018-0243-7.
Thomas, Dennis G., Smith, Jordan N., Thrall, Brian D., Baer, Donald R., Jolley, Hadley, Munusamy, Prabhakaran, Kodali, Vamsi, Demokritou, Philip, Cohen, Joel, and Teeguarden, Justin G. Thu . "ISD3: a particokinetic model for predicting the combined effects of particle sedimentation, diffusion and dissolution on cellular dosimetry for in vitro systems". United States. doi:10.1186/s12989-018-0243-7.
@article{osti_1439688,
title = {ISD3: a particokinetic model for predicting the combined effects of particle sedimentation, diffusion and dissolution on cellular dosimetry for in vitro systems},
author = {Thomas, Dennis G. and Smith, Jordan N. and Thrall, Brian D. and Baer, Donald R. and Jolley, Hadley and Munusamy, Prabhakaran and Kodali, Vamsi and Demokritou, Philip and Cohen, Joel and Teeguarden, Justin G.},
abstractNote = {The development of particokinetic models describing the delivery of insoluble or poorly soluble nanoparticles to cells in liquid cell culture systems has improved the basis for dose-response analysis, hazard ranking from high-throughput systems, and now allows for translation of exposures across in vitro and in vivo test systems. Complimentary particokinetic models that address processes controlling delivery of both particles and released ions to cells, and the influence of particle size changes from dissolution on particle delivery for cell-culture systems would help advance our understanding of the role of particles ion dosimetry on cellular toxicology. We developed ISD3, an extension of our previously published model for insoluble particles, by deriving a specific formulation of the Population Balance Equation for soluble particles. ISD3 describes the time, concentration and particle size dependent dissolution of particles, their delivery to cells, and the delivery and uptake of ions to cells in in vitro liquid test systems. The model is modular, and can be adapted by application of any empirical model of dissolution, alternative approaches to calculating sedimentation rates, and cellular uptake or treatment of boundary conditions. We apply the model to calculate the particle and ion dosimetry of nanosilver and silver ions in vitro after calibration of two empirical models, one for particle dissolution and one for ion uptake. The results demonstrate utility and accuracy of the ISD3 framework for dosimetry in these systems. Total media ion concentration, particle concentration and total cell-associated silver time-courses were well described by the model, across 2 concentrations of 20 and 110 nm particles. ISD3 was calibrated to dissolution data for 20 nm particles as a function of serum protein concentration, but successfully described the media and cell dosimetry time-course for both particles at all concentrations and time points. We also report the finding that protein content in media has effects both on the initial rate of dissolution and the resulting near-steady state ion concentration in solution.},
doi = {10.1186/s12989-018-0243-7},
journal = {Particle and Fibre Toxicology},
number = 1,
volume = 15,
place = {United States},
year = {Thu Jan 25 00:00:00 EST 2018},
month = {Thu Jan 25 00:00:00 EST 2018}
}