Date of Award
Master of Science (MS)
Biomedical and Chemical Engineering
Bisphosphonate Nanoparticles, Inflammation, Osteoarthritis, PEG-PLGA, Polymeric Microparticles, Zoledronic Acid
Biomedical Engineering and Bioengineering | Engineering
Osteoarthritis (OA), a disease caused by wearing and tearing of articular cartilage, affectsover 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. However, ZA is rapidly cleared from the joint after systemic or localized direct injection into the joint. In this study we aim to design polyethylene glycol -b- poly (lactic-co-glycolic acid) (PEG-PLGA) microparticles loaded with a bisphosphonate drug, zoledronic acid to target activated synovial macrophages in an OA affected joint after direct injection into the joint. The PEG-PLGA microparticles were synthesized through phase separation and co-flow technique. Needle size, flow rate, and concentration of continuous phase composed of polyvinyl alcohol, and discontinuous phase composed of dichloromethane was varied to obtain particles ranging from 7 – 42 μm. Further calcium-zoledronic (Ca-ZA) acid nanoparticles were synthesized via reverse microemulsion method and characterized using dynamic light scattering (DLS) and transmission electron microscope (TEM). The average size of Ca-ZA nanoparticles was 114 - 249 nm. Further studies are under way to encapsulate Ca-ZA in microparticles, study release of ZA from microparticles, and targeting efficiency for macrophages.
Espiritusanto, Yohely Maria, "Fabrication of Polymeric Microparticles Loaded With Zoledronic Acid to Treat Osteoarthritis" (2022). Theses - ALL. 629.
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