Nanoparticles Targeting at Inflammation Site

This thesis presents the development and translational evaluation of advanced nanoparticle-based drug delivery systems designed for the sustained and localized delivery of hydrophobic therapeutics, with a focus on pazopanib. Addressing key challenges in drug solubility, stability, and scalable manufacturing, this work explores polymeric, lipid-based, and peptide-modified nanocarriers tailored for chronic disease applications. In the context of osteoarthritis (OA)-associated pain, two classes of biodegradable polymeric nanoparticles—PEG-b-PCL and PLGA—were investigated for their distinct drug release kinetics. PEG-b-PCL enabled prolonged, near zero-order release, whereas PLGA exhibited a rapid burst release. These insights informed the development of a clinically translatable formulation, PEG-PCL-NanoPaz-t, produced via flash nanoprecipitation followed by spray drying. This scalable approach achieved over a 9,000-fold increase in production rate and maintained the therapeutic efficacy of pazopanib in a canine OA model, demonstrating extended pain relief and improved drug solubility. In parallel, the formulation and stability of lipid nanoparticles (LNPs) were enhanced through rational surface engineering. A comparative study between conventional PEG-lipids and zwitterionic peptide–lipid conjugates revealed that C(EK)₄-modified LNPs significantly improved membrane integrity and reduced enzymatic degradation, as demonstrated by synchrotron-based X-ray scattering. These EK4-modified LNPs successfully encapsulated pazopanib and exhibited long-term colloidal stability, suggesting their potential application in targeted renal carcinoma therapy. Collectively, this work highlights how material-driven design can overcome pharmacological and manufacturing bottlenecks in nanoparticle drug delivery. The results contribute broadly to the development of robust nanocarriers for chronic disease treatment, supporting future clinical translation.

Author dc:creator

• Shiyu Du (1360161)

• osteoarthritis
• polymeric nanoparticle
• pazopanib

Statement dc:rights

• In Copyright

DOI dc:identifier

https://doi.org/10.25417/uic.30425128.v1

OAI identifier oai:identifier

oai:figshare.com:article/30425128