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Physiologically based pharmacokinetic modeling of nanoparticles in rodents
Descriptive
TitleInfo
Title
Physiologically based pharmacokinetic modeling of nanoparticles in rodents
Name
(type = personal)
NamePart
(type = family)
Li
NamePart
(type = given)
Xiaowan
NamePart
(type = date)
1991-
DisplayForm
Xiaowan Li
Role
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(authority = RULIB)
author
Name
(type = personal)
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Roth
NamePart
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Charles M
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Charles M Roth
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Advisory Committee
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chair
Name
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Rutgers University
Role
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degree grantor
Name
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Graduate School - New Brunswick
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school
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Text
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theses
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2017
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2017-01
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2017
Place
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xx
Language
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eng
Abstract
(type = abstract)
A variety of nanoparticles are under development for medicine, energy, food and cosmetics. Both organic and inorganic nanoparticles are playing an increased role in industrial and medical applications. However, little is known about their distribution and effects on the human body, and as a result concerns exist about potential health risks and safety problems. The long-term aim of this research is to quantify the distribution characteristics of nanoparticles and explore how the physicochemical properties of nanoparticles influence their distribution. A physiologically based pharmacokinetic (PBPK) model was successfully developed to describe the pharmacokinetics and biodistribution of nanoparticles in various tissues and blood of the body. A PBPK model based on permeability-limited distribution from the vasculature to tissue spaces was compared with the PBPK model based on flow-limited distribution using literature values for distribution of nanoparticles. In general, the blood-flow limited model is not accurate enough to explain the complete biodistribution of nanoparticles, whereas the permeability-flow limited model provides a more faithful simulation. We also applied a novel formulation of the PBPK model, in which blood plasma kinetics are decoupled from tissue kinetics, and compared the description to those of traditional, coupled PBPK models. Our model parameterization suggested that the decoupled model method without elimination based on permeability-flow limited model accurately predicted the trends of nanoparticles concentration in both tissue and blood. This could indicate that partition coefficients of tissues combining with blood flow to tissue might have a great influence on the biodistribution of nanoparticles. This work provides a foundation for more accurate PBPK correlation of nanoparticle biodistribution that should be of utility both in the emerging area of nanotoxicology and in the preclinical drug development of nanomedicines.
Subject
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Topic
Chemical and Biochemical Engineering
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Rutgers University Electronic Theses and Dissertations
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ETD_7855
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electronic resource
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application/pdf
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text/xml
Extent
1 online resource (vii, 26 p. : ill.)
Note
(type = degree)
M.S.
Note
(type = bibliography)
Includes bibliographical references
Subject
(authority = ETD-LCSH)
Topic
Pharmacokinetics
Subject
(authority = ETD-LCSH)
Topic
Nanoparticles
Note
(type = statement of responsibility)
by Xiaowan Li
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TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
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rucore19991600001
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NjNbRU
Identifier
(type = doi)
doi:10.7282/T3WS8WPV
Genre
(authority = ExL-Esploro)
ETD graduate
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Rights
RightsDeclaration
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The author owns the copyright to this work.
RightsHolder
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Name
FamilyName
Li
GivenName
Xiaowan
Role
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Permission or license
DateTime
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2017-01-11 16:49:39
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Name
Xiaowan Li
Role
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Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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2017-01-13T04:13:11
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2017-01-13T04:13:11
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