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Comparing WZB117-liposome Synthesis via Thin-film Hydration and Microfluidic Methods
Yaramiree, Atena
Yaramiree, Atena
Date
2025-11
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Advisor
Type
Thesis
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35.232-2025.60a Atena Yaramiree.pdf
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Description
A Master of Science thesis in Biomedical Engineering by Atena Yaramiree entitled, “Comparing WZB117-liposome Synthesis via Thin-film Hydration and Microfluidic Methods”, submitted in Novemer 2025. Thesis advisor is Dr. Ghaleb Husseini and thesis co-advisor is Dr. Mohamed Abdelgawad. Soft copy is available (Thesis, Completion Certificate, Approval Signatures, and AUS Archives Consent Form).
Abstract
WZB117 is a small-molecule GLUT1 inhibitor that exploits tumor glucose dependence and serves as a targeting ligand. This study evaluates whether thin-film hydration or microfluidic synthesis produces liposomes that are more stable, WZB117-targeted, and ultrasound-responsive. Methods: Control liposomes and WZB117 conjugated liposomes were prepared using thin-film hydration and a 3D serpentine microfluidic mixer at various total flow rates (500, 1000, and 1632 μL/min) and flow rate ratios (5:1, 10:1, 50:1). Calcein was encapsulated, size and polydispersity index (PDI) were measured by dynamic light scattering (DLS), conjugation was confirmed by Fourier-transform infrared spectroscopy (FTIR), lipid content was quantified using the Stewart assay, stability was monitored for 13 weeks at 4 °C, and release under low-frequency ultrasound (6.2, 9, and 10 mW cm⁻²) was modeled using different kinetic orders. Results: Thin-film hydration yielded stable control and WZB117 liposomes with average diameters of approximately 200 nm and low PDI over 13 weeks. Microfluidic control liposomes were smaller and tunable: 5:1, 172–188 nm; 10:1, 127–137 nm; 50:1, 62 nm. Microfluidic WZB117 liposomes also decreased in size with higher flow rate ratios but exhibited time-dependent growth and increased PDI, indicating reduced stability. Ultrasound-triggered intensity-dependent release was observed in all groups, with higher cumulative fractional release (CFR) at 9–10 mW cm ² compared to 6.2 mW cm⁻², and first-order kinetics provided the best fit (R² ≈ 0.99). In conclusion, thin-film hydration is more reliable for producing stable WZB117-targeted carriers, while microfluidics is advantageous for generating well-defined, scalable non-targeted liposomes but requires further optimization for conjugated systems.