Date of Award

5-10-2026

Date Published

June 2026

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Biomedical and Chemical Engineering

Advisor(s)

Era Jain

Keywords

Bisphosphonate Nanoparticles;Inflammation;Osteoarthritis;PEG-PLGA;Polymeric Microparticles;Zoledronic Acid

Abstract

Osteoarthritis (OA), a disease caused by the wearing and tearing of articular cartilage, affects over 32.5 million Americans. Synovial inflammation is now recognized as a major contributor to OA progression and pain. Activated synovial macrophages in an OA joint are believed to play a major role in low-grade inflammation found in OA. Bisphosphonates such as zoledronic acid (ZA) are known to induce apoptosis specifically in macrophages and several of them are being evaluated as a disease-modifying osteoarthritis drug in clinical trials. Zolendroic Acid (Zol) is a biphosphonate that is most commonly used for treatments in bone-related diseases. Previous research reported the use of Zol for therapeutic treatments through encapsulation in nanoparticles. Nanoparticles (NPs) serve as carriers of any cargo to deliver them to a target site. These Zol NPs demonstrated potential in drug delivery, but suffer from constraints in clearance in the body, high-burst releases, and inadvertent cytotoxicity. Microparticles (MPs) fabricated from polyethylene glycol-poly (lactic acid- co-glycolic acid) block polymers (PEG-PLGA) are widely used as drug delivery carriers due to their biocompatibility, targeted delivery, and sustained release properties. In our new Nanoparticle-in-Microparticle (NiM) system, drug-loaded Zol NPs are encapsulated inside larger MPs. This “particle-within-particle” design allows controlled, sustained release kinetics compared to conventional NPs. In this study, by systematically varying polymer concentration, we aim to optimize the fabrication formulations of this NiM system. We investigate how these formulations influence drug loading, encapsulation, and release kinetics. Understanding these relationships allows us to design customized NiM systems tailored for different therapeutic timelines, carrier cargo, and disease environments.

Access

Open Access

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