Identifier

etd-08172015-135151

Degree

Doctor of Philosophy (PhD)

Department

Chemistry

Document Type

Dissertation

Abstract

The potential is great for liposome drug delivery systems that provide specific contents release at diseased tissue sites upon activation by upregulated enzymes; however, this potential will only come to fruition with mechanistic knowledge of the contents release process. NAD(P)H:quinone oxidoreductase type 1 (NQO1) is a target for reductively-responsive liposomes, as it is an enzyme upregulated in numerous cancer tissues and is capable of reducing quinone propionic acid (QPA) trigger groups to hydroquinones that self-cleave from dioleolylphosphatidylethanolamine (DOPE) liposome surfaces, thereby initiating contents release. This research targets the development of analytical methodologies to observe and characterize the dynamics and resulting phase change of the QPA-DOPE liposomal system. It is known that after reduction, QPA-DOPE vesicles aggregate and that the aggregation is correlated with release of their encapsulated contents. While postulated, the final phase identity of this system has not been identified as the conventional methods used to make this measurement are not capable of studying such a unique and dynamic system. Presented herein are the analytical methods, both developed and adapted, which have been used to investigate a liposomal system capable of redox stimulated contents release. The purpose of this work was to utilize these tools to (1) study the terminal phase identity of QPA-DOPE vesicles after reduction, (2) manipulate the QPA-DOPE liposomal system for triggerable inter-vesical fusion, and (3) investigate the liposome bilayer behavior post-reduction and pre-release. The findings of this work are presented and their significance discussed.

Date

2015

Document Availability at the Time of Submission

Secure the entire work for patent and/or proprietary purposes for a period of one year. Student has submitted appropriate documentation which states: During this period the copyright owner also agrees not to exercise her/his ownership rights, including public use in works, without prior authorization from LSU. At the end of the one year period, either we or LSU may request an automatic extension for one additional year. At the end of the one year secure period (or its extension, if such is requested), the work will be released for access worldwide.

Committee Chair

McCarley, Robin L.

Included in

Chemistry Commons

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