Identifier

etd-06052012-091104

Degree

Master of Science (MS)

Department

Chemistry

Document Type

Thesis

Abstract

ABSTRACT Stimuli-responsive liposome systems that utilize endogenous triggers of tumor microenvironment have generated great attention in recent drug delivery research. Among such formulations, redox-responsive liposomes seem highly promising for cancer treatment due to their potential to release high drug concentrations upon reduction (by reductase enzymes). The research described in this thesis involved the evaluation of kinetics of trimethyl-lock quinone propionic acid reduction and lactonization, which accounts for payload release from trimethyl-lock quinone propionic acid-decorated liposomes. To achieve the ultimate goal of this research, several trimethyl-lock quinone propionic acid-based amide compounds were synthesized and characterized. Kinetic studies were carried out with 1H NMR spectroscopy under different experimental conditions, and time-resolved 1H NMR spectra were used to evaluate the kinetic rate constant (k) and half-life time (t½) values for the lactonization (cyclization) reaction. Upon reduction, five different quinone ring-substituted quinone propionic acid-ethanolamine derivatives have shown distinct cyclization rates, representing the influence of ring substituent on lactonization. Tertiary amides, and organic solution conditions, slow down the cyclization process, whereas buffer conditions and higher temperature enhanced the trimethyl-lock lactonization. The outcome of this research can be utilized to optimize redox-responsive trimethyl-lock quinone propionic acid based liposomes, as well as other effective target delivery systems, in order to achieve efficient payload release.

Date

2012

Document Availability at the Time of Submission

Release the entire work immediately for access worldwide.

Committee Chair

McCarley, Robin L.

Included in

Chemistry Commons

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