Biomedical Sciences ETDs

Publication Date

Spring 1-14-2018

Abstract

The prospects of nanoparticle-based drug delivery and imaging have been hindered by insufficient understanding of the effects of nanoparticle physicochemical properties on their in vivo disposition. Here, we present an integrative mathematical modeling and in vivo imaging approach to quantify the relationship between nanoparticle physicochemical properties, namely, size, surface charge, and surface chemistry, on their in vivo disposition kinetics in healthy rats. We developed simple master equations in closed-form to accurately represent the time-dependent concentration of nanoparticles in different regions of the body and obtain functional relationships for predictive purpose to support rational design of nanomedicine. We further used the observations of the in vivo study to inform a hybrid multiscale mathematical model to predict the global biodistribution of nanoparticles in the body and the spatiotemporal evolution of nanoparticles inside a simulated 2D tumor. The model is supposed to be an in silico tool to predict the effect of particle properties on biodistribution and clearance of nanoparticles and suggest design guidelines for optimizing the distribution to the target site.

Keywords

nanomedicine, pharmacokinetics, cancer, mathematical modeling, SPECT imaging, random walk

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

Elaine L. Bearer

Second Committee Member

Vittorio Cristini

Third Committee Member

C. Jeffrey Brinker

Fourth Committee Member

Bridget S. WIlson

Fifth Committee Member

Zhihui Wang

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