ISD3: a particokinetic model for predicting the combined effects of particle sedimentation, diffusion and dissolution on cellular dosimetry for in vitro systems
Abstract Background 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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-01-01
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| Series: | Particle and Fibre Toxicology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12989-018-0243-7 |
| _version_ | 1828403166621728768 |
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| author | Dennis G. Thomas Jordan N. Smith Brian D. Thrall Donald R. Baer Hadley Jolley Prabhakaran Munusamy Vamsi Kodali Philip Demokritou Joel Cohen Justin G. Teeguarden |
| author_facet | Dennis G. Thomas Jordan N. Smith Brian D. Thrall Donald R. Baer Hadley Jolley Prabhakaran Munusamy Vamsi Kodali Philip Demokritou Joel Cohen Justin G. Teeguarden |
| author_sort | Dennis G. Thomas |
| collection | DOAJ |
| description | Abstract Background 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 and 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. Results 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. We applied 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. 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 affects the initial rate of dissolution and the resulting near-steady state ion concentration in solution for the systems we have studied. Conclusions By combining experiments and modeling, we were able to quantify the influence of proteins on silver particle solubility, determine the relative amounts of silver ions and particles in exposed cells, and demonstrate the influence of particle size changes resulting from dissolution on particle delivery to cells in culture. ISD3 is modular and can be adapted to new applications by replacing descriptions of dissolution, sedimentation and boundary conditions with those appropriate for particles other than silver. |
| first_indexed | 2024-12-10T10:13:18Z |
| format | Article |
| id | doaj.art-fc7a0e6e6d464a539c4283ced0eed268 |
| institution | Directory Open Access Journal |
| issn | 1743-8977 |
| language | English |
| last_indexed | 2024-12-10T10:13:18Z |
| publishDate | 2018-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Particle and Fibre Toxicology |
| spelling | doaj.art-fc7a0e6e6d464a539c4283ced0eed2682022-12-22T01:53:04ZengBMCParticle and Fibre Toxicology1743-89772018-01-0115112210.1186/s12989-018-0243-7ISD3: a particokinetic model for predicting the combined effects of particle sedimentation, diffusion and dissolution on cellular dosimetry for in vitro systemsDennis G. Thomas0Jordan N. Smith1Brian D. Thrall2Donald R. Baer3Hadley Jolley4Prabhakaran Munusamy5Vamsi Kodali6Philip Demokritou7Joel Cohen8Justin G. Teeguarden9Computational Biology, Biological Sciences Division, Pacific Northwest National LaboratoryHealth Effects and Exposure Science, Biological Sciences Division, Pacific Northwest National LaboratoryHealth Effects and Exposure Science, Biological Sciences Division, Pacific Northwest National LaboratoryInterfacial Sciences and Simulation, Environmental Molecular Sciences Division, Pacific Northwest National LaboratoryHealth Effects and Exposure Science, Biological Sciences Division, Pacific Northwest National LaboratoryInterfacial Sciences and Simulation, Environmental Molecular Sciences Division, Pacific Northwest National LaboratoryHealth Effects and Exposure Science, Biological Sciences Division, Pacific Northwest National LaboratoryCenter for Nanotechnology and Nanotoxicology, Department of Environmental Health, Harvard University T. H. Chan School of Public HealthCenter for Nanotechnology and Nanotoxicology, Department of Environmental Health, Harvard University T. H. Chan School of Public HealthHealth Effects and Exposure Science, Biological Sciences Division, Pacific Northwest National LaboratoryAbstract Background 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 and 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. Results 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. We applied 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. 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 affects the initial rate of dissolution and the resulting near-steady state ion concentration in solution for the systems we have studied. Conclusions By combining experiments and modeling, we were able to quantify the influence of proteins on silver particle solubility, determine the relative amounts of silver ions and particles in exposed cells, and demonstrate the influence of particle size changes resulting from dissolution on particle delivery to cells in culture. ISD3 is modular and can be adapted to new applications by replacing descriptions of dissolution, sedimentation and boundary conditions with those appropriate for particles other than silver.http://link.springer.com/article/10.1186/s12989-018-0243-7NanoparticleDissolutionPopulation balance equationNanosilverIn vitro dosimetryParticokinetic model |
| spellingShingle | Dennis G. Thomas Jordan N. Smith Brian D. Thrall Donald R. Baer Hadley Jolley Prabhakaran Munusamy Vamsi Kodali Philip Demokritou Joel Cohen Justin G. Teeguarden ISD3: a particokinetic model for predicting the combined effects of particle sedimentation, diffusion and dissolution on cellular dosimetry for in vitro systems Particle and Fibre Toxicology Nanoparticle Dissolution Population balance equation Nanosilver In vitro dosimetry Particokinetic model |
| title | ISD3: a particokinetic model for predicting the combined effects of particle sedimentation, diffusion and dissolution on cellular dosimetry for in vitro systems |
| title_full | ISD3: a particokinetic model for predicting the combined effects of particle sedimentation, diffusion and dissolution on cellular dosimetry for in vitro systems |
| title_fullStr | ISD3: a particokinetic model for predicting the combined effects of particle sedimentation, diffusion and dissolution on cellular dosimetry for in vitro systems |
| title_full_unstemmed | ISD3: a particokinetic model for predicting the combined effects of particle sedimentation, diffusion and dissolution on cellular dosimetry for in vitro systems |
| title_short | ISD3: a particokinetic model for predicting the combined effects of particle sedimentation, diffusion and dissolution on cellular dosimetry for in vitro systems |
| title_sort | isd3 a particokinetic model for predicting the combined effects of particle sedimentation diffusion and dissolution on cellular dosimetry for in vitro systems |
| topic | Nanoparticle Dissolution Population balance equation Nanosilver In vitro dosimetry Particokinetic model |
| url | http://link.springer.com/article/10.1186/s12989-018-0243-7 |
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