Author ORCID Identifier

https://orcid.org/0000-0001-7103-7634

Author Linked-In Account

https://www.linkedin.com/in/dr-madhumithra-thangadurai-bb7b39257/

Date of Award

17-8-2025

Document Type

Thesis

School

School of Chemical & Biotechnology

Programme

Ph.D.-Doctoral of Philosophy

First Advisor

Dr.S.Anuradha

Keywords

Drug Delivery, Nanomicelle, Rheumatoid arthritis, Invasive Fibroblast-like-synoviocytes, Inflamed synovium

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease marked by persistent synovial inflammation, progressive cartilage and bone destruction, and systemic complications. 1% of the global population are affected by RA, when their immune system targets synovial tissues, leading to joint pain, swelling, and functional disability. Standard treatments, such as disease-modifying antirheumatic drugs (DMARDs) like methotrexate (MTX), are limited by systemic toxicity and inconsistent patient responses, highlighting the need for improved therapies. This research work explores protein-glycosaminoglycan nanomicelles engineered using Zein with Chondroitin or carboxymethylated Dextran Sulfate as targeted drug delivery vehicles for RA.

MTX was encapsulated within these nanomicelles to enhance joint-specific delivery and therapeutic efficacy. In vitro studies using a 2D RA model with inflammatory synovial cells demonstrated that the nanomicelles selectively reduced cell migration and invasion. In vivo evaluation using Complete Freund’s Adjuvant-induced RA rat model showed that MTXloaded nanomicelles effectively preserved bone and trabecular quality as confirmed by microCT.

Histopathology has confirmed the minimized synovial inflammation, bone erosion, cartilage component and less systemic toxicity. These findings support protein-GAG nanomicelles as a promising precision therapy for RA, offering targeted delivery, reduced side effects, and improved outcomes, with robust preclinical validation for future clinical translation.

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