Date of Award


Degree Type


Degree Name

Master of Engineering Science


Biomedical Engineering


Dr. Wankei Wan

Second Advisor

Dr. Beth Gillies

Third Advisor

Dr. Jeff Hutter


Unilamellar vesicles (ULVs) are effective drug delivery vehicles used to encapsulate therapeutic agents. Growing interest of their use in the pharmaceutical sciences is a result of their reported ability to enhance therapeutic efficacy at low doses, increase the half life of administered agents, and provide site targeted delivery. Since their initial synthesis in 1965 by Bangham et al., a variety of methods for producing ULVs have been proposed and investigated. Recently, a spontaneously forming ULV was reported using a combination of natural phospholipids: dimyristoyl-phosphatidylcholine (DMPC), dimyristoylphosphatidylglycerol (DMPG) and dihexanoyl-phosphatidylcholine (DHPC). This system offers great potential as a controlled release system due to its finite size control, narrow size distribution, batch-to-batch reproducibility, ease of preparation and shelf life stability. This research focuses on (1) the ability to form these ULVs and characterize them using smallangle neutron scattering (SANS) and cryogenic transmission electron microscopy (cryo- TEM); (2) the ability to control their size and size distribution by varying charge density, total lipid concentration, and annealing rate; (3) the stability of these ULVs once formed with respect to dilution factor and (4) the precursor bicelle structure, its growth, and role in the end-state vesicle. The spontaneous formation of ULVs was successfully identified using both SANS and cryo-TEM. Results indicated that they existed only within a narrow window of charge densities, where larger size ULVs could be obtained at a lower charge density through slow temperature annealing. By varying the annealing rate and charge density, a six-fold change in mean radius of the ULVs was observed. The time-resolved bicelle experiments showed that the size of the nano-disks increased continuously due to disk interactions where their coalescence was best described by a power law relationship with time. Overall, the growth rate increased with increasing temperature and ionic strength and decreased with total lipid concentration, whereas the size of the end-state ULV increased with increasing annealing temperature, ionic strength and total lipid concentration. Finally, the stability of these ULVs was confirmed through a series of high temperature dilution experiments. This work contributes to the basic understanding of ULV formation, methods of controlling the size and stability offering insight for applications as a potential nano-carrier system.



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