Date of Award:

8-2020

Document Type:

Thesis

Degree Name:

Master of Science (MS)

Department:

Biological Engineering

Committee Chair(s)

David Britt

Committee

David Britt

Committee

Elizabeth Vargis

Committee

Brett L. Hurst

Abstract

Congenital cytomegalovirus (CMV) is the leading viral cause of birth defects worldwide and leads to a variety of complications. Ganciclovir is the most common anti-CMV drug used but often causes severe side effects. Quercetin, a plant pigment, shows anti-CMV activity that may provide a less toxic alternative to ganciclovir, or when co-administered, reduce ganciclovir treatments. However, a drug carrier is needed to deliver quercetin for CMV treatment. In this study, three Pluronic polymers (P123, F127, and F68) were investigated as a quercetin drug delivery system (DDS) for CMV treatment.

All selected Pluronics successfully encapsulated quercetin at varying degrees of efficacy. Pluronic P123 was the most efficient (92.8%), F127 was intermediate (12.8%), and F68 was the least efficient (1.8%). Anti-CMV activity and cell toxicity of each DDS were tested. Subsequent adjustment to composition and quercetin loading was performed to maximize viral inhibition and minimize toxicity. It was found that F68 loaded at 75% of maximum quercetin capacity was the optimal CMV inhibitor.

Furthermore, ganciclovir and the Pluronic F68 DDS were administered together in an attempt to reduce the ganciclovir needed to treat CMV. When administered together, 1000X less ganciclovir was needed. Supplementation of ganciclovir with Pluronic F68 DDS could reduce side effects and treatment regimen costs.

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