Graduation Date

Summer 8-13-2021

Document Type

Thesis

Degree Name

Master of Science (MS)

Programs

Pharmaceutical Sciences

First Advisor

Dr. Dong Wang

Abstract

Inflammation is a natural response of the body to infections or any potential threat to the body. But, sometimes the immune system attacks its own body causing persistent inflammation leading to inflammatory diseases. One of the common chronic inflammatory diseases is rheumatoid arthritis (RA) which causes inflammation of the synovial membrane. The current treatments for RA are effective in controlling the symptoms but they come with severe side effects and economic burden. Further, the management of pain is still a problem with these drugs. Sinomenine is a natural alkaloid obtained from the Chinese medicinal plant Sinomenium acutum that has been used to clinically treat RA for several years in China. They exhibit various pharmacological effects like anti-inflammatory, anti-arthritis, and analgesic effects, etc. which makes it favorable in treating rheumatic diseases. Yet again, sinomenine has some disadvantages like poor bioavailability, short half-life, and systemic toxicity, etc. Therefore, in this thesis we concentrated on developing a macromolecular prodrug of sinomenine and evaluated its therapeutic and analgesic efficacy in an animal model of monoarticular antigen-induced arthritis (MAA). To address the current drawbacks of sinomenine, we developed this macromolecular prodrug as a thermoresponsive hydrogel and administered it to the animals by intra-articular injection. We showed that the HPMA copolymer sinomenine can form hydrogel and can be retained in the knee joint for a span of twenty-one days. The results from the pain evaluation tests also confirmed their potential to exhibit local analgesic effects without any potential toxicity. They also demonstrated the absence of spinal cord analgesia which helps prevent tolerance and addiction. We can conclude from these results that this macromolecular prodrug of sinomenine may have a potential for the management of pain in RA.

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