Redox-active Liposome Delivery Agents With Highly Controllable Stimuli-responsive Behavior
type: CreativeWork
description: Over the last few decades, liposomes have generated a lot of interest as drug delivery vehicles to address the need for providing both increased therapeutic efficacy and decreased systemic exposure, simultaneously. The challenge of increasing drug accumulation at diseased sites, without compromising the integrity and stability of the liposomal carrier during circulation, has been met with two possible solutions: (1) active targeting and (2) active triggering. To achieve selective and site-specific delivery of drugs to tumors, active triggering methods have been developed wherein a responsive element is incorporated into the liposomal bilayer, which causes destabilization of the liposome upon exposure to the proper stimulus. Endogenous stimuli can offer high specificities and sensitivities, if appropriate trigger groups exist so as to take full advantage of diseased site characteristics. The research described herein involved the synthesis of redox-active, quinone-lipid conjugates that were prepared into liposomes for the containment and subsequent triggered release of encapsulated cargo. Development of said system required (1) the synthesis and then characterization of various simple quinones and quinone propionic acids by cyclic voltammetry and X-ray crystallography and (2) the preparation of substituted quinone dioleoylphosphatidylethanolamine lipids into liposomes and evaluation of their triggered release behaviors by fluorescence emission spectrometry. Elucidation of the electrochemical properties of simple quinones and quinone propionic acids revealed a correlation between quinone substitution and reduction potential, meaning that the electronics of the quinone trigger can be adjusted through their chemical structure. X-ray crystallography showed a highly distorted quinone ring proximal to the trimethyl-locked propionic acid side chain. Upon introduction of a chemical reducing agent, the four different substituted quinone-dioleoylphosphatidylethanolamine liposo…
abstract: Over the last few decades, liposomes have generated a lot of interest as drug delivery vehicles to address the need for providing both increased therapeutic efficacy and decreased systemic exposure, simultaneously. The challenge of increasing drug accumulation at diseased sites, without compromising the integrity and stability of the liposomal carrier during circulation, has been met with two possible solutions: (1) active targeting and (2) active triggering. To achieve selective and site-specific delivery of drugs to tumors, active triggering methods have been developed wherein a responsive element is incorporated into the liposomal bilayer, which causes destabilization of the liposome upon exposure to the proper stimulus. Endogenous stimuli can offer high specificities and sensitivities, if appropriate trigger groups exist so as to take full advantage of diseased site characteristics. The research described herein involved the synthesis of redox-active, quinone-lipid conjugates that were prepared into liposomes for the containment and subsequent triggered release of encapsulated cargo. Development of said system required (1) the synthesis and then characterization of various simple quinones and quinone propionic acids by cyclic voltammetry and X-ray crystallography and (2) the preparation of substituted quinone dioleoylphosphatidylethanolamine lipids into liposomes and evaluation of their triggered release behaviors by fluorescence emission spectrometry. Elucidation of the electrochemical properties of simple quinones and quinone propionic acids revealed a correlation between quinone substitution and reduction potential, meaning that the electronics of the quinone trigger can be adjusted through their chemical structure. X-ray crystallography showed a highly distorted quinone ring proximal to the trimethyl-locked propionic acid side chain. Upon introduction of a chemical reducing agent, the four different substituted quinone-dioleoylphosphatidylethanolamine liposo…
author: Carrier, Nicole Hollabaugh
keywords: liposomes, quinones, redox, drug delivery
date published: 2011-01-01T08:00:00Z
date modified: 2026-07-24T02:59:03Z
provider: Lousiana State University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Chemistry

PropertyValue
property ID: DOI
value: 10.31390/gradschool_dissertations.1147