Electronic Theses and Dissertations

Date

2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Chemistry

Committee Chair

Tomoko Fujiwara

Committee Member

Jessica Jennings

Committee Member

Joel Bumgardner

Committee Member

Tanei Ricks

Committee Member

Timothy Brewster

Abstract

This dissertation outlines a novel triple-networked hydrogel for a hydrophobic drug delivery system. The drug Simvastatin is used as a cardiovascular medication, but it has also been reported to function as an osteoinductive agent. Therefore, to deliver the drug locally to the affected area, a mechanically stable and tunable hydrogel has been designed using modified chitosan, PEGDMA, and PLA-PEG micelles. This hydrogel exhibited a steady release of simvastatin over a long period of 14 weeks. Additionally, the hydrogel is biocompatible and biodegradable, as demonstrated by the cytotoxicity test. This dissertation presents a comprehensive exploration of a novel triple-networked hydrogel specifically designed for an innovative hydrophobic drug delivery system. The focus of this research is on delivering drugs from a hydrogel locally. In my research, one of the drugs studied is simvastatin, a drug widely used for cardiovascular treatment, which has also gained attention for its potential as an osteoinductive agent. To facilitate the localized delivery of this vital medication to targeted areas, a mechanically stable and tunable hydrogel was meticulously designed. This hydrogel incorporates modified chitosan, PEGDMA, and PLA-PEG micelles in its formulation, showcasing its potential in drug release applications. The hydrogel demonstrates a remarkable capability for sustained drug release, maintaining a steady output of simvastatin over an extended duration of 14 weeks. Importantly, the biocompatibility and biodegradability of this hydrogel were affirmed through rigorous cytotoxicity testing, confirming its safety for pharmaceutical applications. Another intriguing dimension of this research examines the conjugation of zinc, a metal known for its essential biological roles, with curcumin, a naturally occurring molecule celebrated for its numerous therapeutic benefits. Curcumin's ability to chelate with various metals enhances its bioactivity, thus the conjugation process allows for the synergistic delivery of both zinc and the curcumin complex, potentially magnifying therapeutic outcomes. The study meticulously investigates the properties of the curcumin-zinc complex within diverse media, encompassing both aqueous and organic environments, and under a wide range of conditions, from highly acidic to basic, alongside variations in salt concentrations. To achieve this, a variety of buffered solutions at differing pH levels and concentrations, including acetate, carbonate, phosphate, tris, and borate buffers, were employed. The experimental results unveiled noteworthy dissociation characteristics of the curcumin-zinc complex contingent upon these experimental parameters. A significant finding was the formation of a curcumin-boron compound upon interacting with boron-rich environments. Furthermore, a comprehensive release study was conducted on the curcumin-zinc complex released from the hydrogel, indicating that the dynamics of curcumin and the zinc/curcumin-zinc complex's release are intricately interlinked. Crucially, the study established that the release profile of this complex is sensitive to pH variations. Moreover, the quantity of zinc released from the hydrogel at different pH levels was measured, revealing that its release also exhibits a pronounced pH sensitivity. Collectively, these findings pave the way for the development of advanced hydrogels tailored for long-term drug delivery applications, thereby markedly enhancing the field of metal-curcumin drug delivery and offering promising avenues for future therapeutic innovations.

Comments

Data is provided by the student.

Library Comment

Dissertation or thesis originally submitted to ProQuest.

Notes

Open access

Download

Share

COinS