Graduation Date

Summer 8-26-2024

Document Type

Thesis

Degree Name

Master of Science (MS)

Programs

Pharmaceutical Sciences

First Advisor

Dr Aaron Mohs

Abstract

Bisphosphonates, particularly zoledronic acid (ZA), are crucial in managing bone resorption and treating skeletal disorders like multiple myeloma (MM). While ZA has demonstrated significant anti-myeloma activity in-vitro, its clinical use is limited by poor systemic exposure and potential off-target effects. This thesis investigates two strategies to conjugate polyethylene glycol (PEG) and hyaluronic acid (HA) to ZA to overcome these limitations. The first strategy, targeting the tertiary alcohol group of ZA, faced significant challenges due to the difficulty in conjugation. The second strategy, focusing on the hydroxyl group of the phosphonate moiety in ZA, successfully yielded a ZA-PEG conjugate, enhancing ZA's potency against multiple myeloma cells. Further conjugation with HA aims to improve the targeting capability and therapeutic effectiveness of ZA, enhancing its overall potency in treating multiple myeloma by improving systemic circulation and targetability.

Comments

2024 Copyright, the authors

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Available for download on Saturday, January 04, 2025

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