{"id":{"repo_id":"uic","oai_identifier":"oai:figshare.com:article/30425128"},"canonical_url":"https://search.dev.ndltd.org/etd/uic/oai:figshare.com:article/30425128","repository":{"repo_id":"uic","name":"University of Illinois - Chicago","base_url":"https://api.figshare.com/v2/oai"},"display":{"title":"Nanoparticles Targeting at Inflammation Site","abstract":"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.","abstract_html":"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.","abstract_has_math":false,"creators":["Shiyu Du (1360161)"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-08-01T00:00:00Z","date_published":"2025-08-01T00:00:00Z","updated_at":"2026-07-27T21:34:47Z","subjects":["osteoarthritis","polymeric nanoparticle","pazopanib"],"languages":[],"rights":["In Copyright"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://doi.org/10.25417/uic.30425128.v1","outbound_label":"DOI","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Shiyu Du (1360161)"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-08-01T00:00:00Z"]},{"key":"dc:relation","label":"Dc Relation","values":["https://figshare.com/articles/thesis/Nanoparticles_Targeting_at_Inflammation_Site/30425128"]},{"key":"dc:type","label":"Dc Type","values":["Text","Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["osteoarthritis","polymeric nanoparticle","pazopanib"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["In Copyright"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["10.25417/uic.30425128.v1"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["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."]},{"key":"dc:title","label":"Title","values":["Nanoparticles Targeting at Inflammation Site"]}]}],"canonical_facts":{"dc:creator":["Shiyu Du (1360161)"],"dc:date":["2025-08-01T00:00:00Z"],"dc:description":["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."],"dc:identifier":["10.25417/uic.30425128.v1"],"dc:relation":["https://figshare.com/articles/thesis/Nanoparticles_Targeting_at_Inflammation_Site/30425128"],"dc:rights":["In Copyright"],"dc:subject":["osteoarthritis","polymeric nanoparticle","pazopanib"],"dc:title":["Nanoparticles Targeting at Inflammation Site"],"dc:type":["Text","Thesis"]},"updated_at":"2026-07-27T21:34:47Z"}