Molecular design of nanoparticle-based delivery vehicles for pneumonic plague
type: CreativeWork
description: The work described in this dissertation focuses on the design of polyanhydride nanoparticles that function as both adjuvants and long-term antigen delivery vehicles in order to improve vaccination, specifically for biodefense-related applications. Chapter 1 is an introduction into the threat of bioterrorism, polymer-based controlled delivery systems and challenges associated with vaccine design. Chapter 2 is a detailed literature review of topics related to the research conducted in this dissertation. Areas covered include basic immunology, vaccine design, degradable polymer-based adjuvant engineering, plague (Yersinia pestis) biology, and vaccines that confer protection against plague. Chapter 3 overviews the research objectives and the specific aims of this work. Chapter 4 describes the effect polymer chemistry has on uptake of polyanhydride nanoparticles by THP-1 human monocytic cells. Nanoparticles of similar size, regardless of poly[1,6-bis(p-carboxyphenoxy)hexane-co-sebacic acid] (CPH:SA) copolymer chemistry, were fabricated using a novel anti-solvent precipitation technique. Confocal microscopy revealed that less hydrophobic nanoparticles (SA-rich) were more readily internalized and trafficked by monocytes. Interestingly, exposure to nanoparticles of any chemistry enhanced soluble protein uptake by monocytes over cells exposed to soluble protein alone. Chapter 5 utilizes the combination of population and individual analyses in order to better understand the effect chemistry has on nanoparticle uptake and subsequent activation of dendritic cells. Nanoparticles composed of CPH:SA and poly[1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane-co-CPH] (CPTEG:CPH) were used for this study in order to investigate a wide range of chemistries. Nanoparticles composed of less hydrophobic chemistry were able to activate cell surface marker expression where as nanoparticles composed of more hydrophobic chemistry were able to cause the enhanced secretion of cytokines. Using confocal …
abstract: The work described in this dissertation focuses on the design of polyanhydride nanoparticles that function as both adjuvants and long-term antigen delivery vehicles in order to improve vaccination, specifically for biodefense-related applications. Chapter 1 is an introduction into the threat of bioterrorism, polymer-based controlled delivery systems and challenges associated with vaccine design. Chapter 2 is a detailed literature review of topics related to the research conducted in this dissertation. Areas covered include basic immunology, vaccine design, degradable polymer-based adjuvant engineering, plague (Yersinia pestis) biology, and vaccines that confer protection against plague. Chapter 3 overviews the research objectives and the specific aims of this work. Chapter 4 describes the effect polymer chemistry has on uptake of polyanhydride nanoparticles by THP-1 human monocytic cells. Nanoparticles of similar size, regardless of poly[1,6-bis(p-carboxyphenoxy)hexane-co-sebacic acid] (CPH:SA) copolymer chemistry, were fabricated using a novel anti-solvent precipitation technique. Confocal microscopy revealed that less hydrophobic nanoparticles (SA-rich) were more readily internalized and trafficked by monocytes. Interestingly, exposure to nanoparticles of any chemistry enhanced soluble protein uptake by monocytes over cells exposed to soluble protein alone. Chapter 5 utilizes the combination of population and individual analyses in order to better understand the effect chemistry has on nanoparticle uptake and subsequent activation of dendritic cells. Nanoparticles composed of CPH:SA and poly[1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane-co-CPH] (CPTEG:CPH) were used for this study in order to investigate a wide range of chemistries. Nanoparticles composed of less hydrophobic chemistry were able to activate cell surface marker expression where as nanoparticles composed of more hydrophobic chemistry were able to cause the enhanced secretion of cytokines. Using confocal …
author: Ulery, Bret
language: en
date published: 2010-01-01
date modified: 2026-07-24T02:39:53Z
provider: Iowa State University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Iowa State University

PropertyValue
property ID: DOI
value: 10.31274/etd-180810-2241