Date of Thesis

Summer 2025

Description

Liposomes, spherical vesicles composed of lipid bilayers, are widely used in drug delivery due to their biocompatibility, biodegradability, and ability to interact with biological membranes. Despite these advantages, liposomes remain moderately unstable systems, highly susceptible to environmental stressors such as pH fluctuations, ionic strength variations, temperature changes, and interactions with other components. Addressing both chemical and physical instability is essential for translating liposomal formulations from experimental formulation to viable pharmaceutical products.

This study investigates the physicochemical characteristics of a mixed-phospholipid system in which one lipid is saturated, and the other is unsaturated (DMPC and DOPC respectively). Liposomes are prepared using thin film hydration, freeze–thaw cycling, and extrusion to yield mostly unilamellar vesicles with diameters of approximately 100 nm. Once prepared, liposomes are exposed to accelerated aging at 70 °C, and aliquots are collected at regular intervals for analysis. Chemical stability was evaluated using high-performance liquid chromatography (HPLC) and lipid peroxidation assays, while physical stability was characterized by dynamic and static light scattering (DLS/SLS), UV–Vis transmittance measurements, and cryogenic transmission electron microscopy (cryo-TEM). Results reveal a strong correspondence between chemical and physical degradation, providing evidence that initial physical changes, such as liposome aggregation and fusion, may play an important role in the onset of chemical degradation and highlighting how subsequent molecular breakdown promotes structural disintegration. This study presents these findings and draws conclusions about the role of lipid composition in controlling liposome stability, offering essential insights for future liposome-based drug delivery system design.

Keywords

liposome stability, phospholipid composition, chemical degradation, physical instability, membrane fusion, lipid oxidation, hydrolytic breakdown, bilayer dynamics, accelerated aging, lipid saturation ratio

Access Type

Masters Thesis

Degree Type

Master of Science in Chemical Engineering

Major

Chemical Engineering

First Advisor

Dr. Kenny Mineart

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