Graduation Date

Summer 8-9-2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Pharmaceutical Sciences

First Advisor

Ram Mahato

Abstract

Alcoholic liver disease is a challenging chronic disease worldwide. Alcohol abuse and subsequent inflammation, oxidative stress, and disordered lipid metabolism result in liver damage. This dissertation aims to develop a reliable therapeutic strategy for alcoholic liver disease treatment. We have employed polymeric nanoparticles as the delivery system to the liver and utilized PDE4B inhibitor as a novel approach for alcoholic liver disease treatment.

Chapter 1 is an overview of alcoholic liver disease, including the background, pathology, risk factors, and current treatment. In addition, the application of PDE4 inhibitors in alcoholic liver disease was discussed, suggesting a promising avenue for future exploration and development.

Chapter 2 describes the nanoparticles delivery of PDE4B inhibitor for alcoholic liver disease treatment. The results proved that nanoformulation alleviated disease in vivo, as demonstrated by improved inflammation, oxidative stress, and lipid metabolism in the liver. The encouraging results indicated the potential of this approach as a novel therapeutic strategy.

Chapter 3 discussed the pharmacokinetics and biodistribution profile of the nanoformulation in comparison to the free drug. The results suggested that the nanoparticle delivery system enhanced the bioavailability and biodistribution of the loaded small molecule in mice. This finding provides supportive evidence for the improved efficacy of nanoparticle formulation.

Chapter 4 is the summary of the key findings of each chapter and the discussion of current limitations and future directions.

Available for download on Sunday, August 02, 2026

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