Nanoscience and Microsystems ETDs

Anh-Dung Le

Publication Date

Summer 7-15-2022

Abstract

Physiologically-based Pharmacokinetics (PBPK) modeling—a mechanistic mathematical tool to predict biodistribution to inform drug development, requires knowledge of the physico-chemical properties of the drug in question as well as the anatomy and physiology of the organism. Unlike with molecular drugs, nanoparticle parameters often need to be estimated by fitting models to time-course data, which can result in large uncertainties in parameter estimates due to a high-dimensional parameter space. Our research addresses this challenge by offering a path to parameter insights using global sensitivity analysis. The first chapter is an overview of the PBPK model structure and mathematical framework used in our study of colloidal gold nanoparticles in mice. The second chapter introduces parameter sieving as a method for model reduction. We show that it is possible to obtain the same goodness-of-fit while excluding estimation of insensitive parameters. The final chapter utilizes time-course sensitivities to suggest drug delivery strategies.

Keywords

Physiologically based pharmackinetic modeling, mathematical biology, pharmacology, colloidal gold nanoparticles

Document Type

Dissertation

Language

English

Degree Name

Nanoscience and Microsystems

Level of Degree

Doctoral

Department Name

Nanoscience and Microsystems

First Committee Member (Chair)

Professor Helen J. Wearing

Second Committee Member

Distinguished Professor David G. Whitten

Third Committee Member

Assistant Professor Dingsheng Li (University of Nevada, Reno)

Fourth Committee Member

Assistant Professor Owen Lewis

Download

Share

COinS