Doctoral Dissertations
Date of Award
5-2022
Degree Type
Dissertation
Degree Name
Doctor of Philosophy
Major
Biomedical Engineering
Major Professor
Elizabeth D Barker
Committee Members
Stephanie Termaath, Susan Spiller, Tao Wu
Abstract
More than 99.9% of patients treated for childhood cancer develop a chronic health conditions by age 50 ,according to a report from the St. Jude Lifetime Cohort Study, where cumulative burden was highest in survivors of CNS [central nervous system] malignancies. Malignant CNS tumors remain the leading cause of death among children diagnosed with cancer and the most common malignant pediatric brain and CNS tumor is medulloblastoma, which has 5-year and 10-year survival rates of 72.3% and 66.8%, respectively.
Chemotherapy is recommended for all medulloblastoma patients and is regarded as an effective form of treatment because of its ability to combat rapidly dividing cells and significantly inhibit disease progression. However, toxicity and exposure to healthy tissues increases risk of severe acute and long-term effects such as neurological sequelae, cardiotoxicity, and lung function. The dose required to treat disease is dependent on the amount of drug able to reach cancer cells and the dwell time within the cancerous tissue, both are limited by barriers in the route of drug delivery to the tumor and within the tumor microenvironment.
Local, controlled drug delivery systems can stimulate therapeutic administration without the need of high dosage and repeated administration while reducing systemic exposure unlike conventional drug administration. Injectable hydrogels synthesized with chemotherapy have potential to localize delivery in medulloblastoma tumor microenvironments, but in a PubMed literature search of “medulloblastoma hydrogels,” very few studies were found.
The purpose of the proposed project is to synthesize, characterize, and evaluate a novel injectable starch-based hydrogel loaded with a conventional drug, doxorubicin, administered locally to treat pediatric medulloblastoma tumors. Hydrogels are three-dimensional polymeric cross-linking networks with the capability of delivering drugs such as hydrophilic and small-molecule drugs while fine-tuning the size, architecture, and function of the gel to control drug release kinetics.
Recommended Citation
Patel, Jenny P, "A Local Drug Delivery Approach for Enhancing Tissue Penetration of Chemotherapy to Improve Treatment Outcomes of Pediatric Brain Tumors. " PhD diss., University of Tennessee, 2022.
https://trace.tennessee.edu/utk_graddiss/11689