Date of Award
Doctor of Philosophy
Kwei-Yu Liu. Ph.D. The University of Memphis. December 2019. Development of Multilayered Micelles and Hydrogels for Drug/Gene Delivery Systems. Major Professor: Tomoko Fujiwara, Ph.D.In recent years, polymeric drug vehicles which respond to external stimuli have attracted extensive attention for delivering their therapeutic payloads at targeted locations and with controlled timing. To realize these smart delivery systems, our strategy is to design polymeric micelles with multilayered morphologies and stimuli-responsive properties as a drug carrier. In this dissertation, the development of two types of drug delivery systems are described. The first approach focuses on a hydrogel system prepared from DNA-loaded three-layered micelles (3LM) composed of biodegradable block copolymers. The 3LM possess great stability under physiological conditions and release DNA in slightly acidic conditions. In this study, 3LM were utilized to achieve thermo-responsive, injectable hydrogel systems for localized gene delivery. Specifically, the structure, stability, mechanical strength, sol-to-gel transition mechanism, and degradation behavior of the hydrogels were analyzed. In vitro studies of the DNA-loaded hydrogels were further discussed for gene delivery capability.The second approach was to design multilayered micelles incorporating poly(amino acid) segments to explore novel mechanisms for efficient drug delivery. We hypothesized that biocompatible poly(amino acid)s would be capable of forming self-assembled micelles via electrostatic interactions and respond to a variety of stimuli including changes in pH, dilution, and salt concentrations. The resulting micelles were characterized and evaluated for drug delivery capabilities.
Dissertation or thesis originally submitted to ProQuest
LIU, KWEIYU, "DEVELOPMENT OF MULTILAYERED MICELLES AND HYDROGELS FOR DRUG/GENE DELIVERY SYSTEMS" (2019). Electronic Theses and Dissertations. 2645.