Doctor of Philosophy (PhD)
The main objective of this research is to further enhance fundamental understanding of drug-delivery vesicles composed of model membranes. For that purpose, the ability of triblock copolymers to form vesicular structures and the shape deformations of the polymer vesicles under external forces have been studied. Further, co-assembly of the triblock copolymers with phospholipids to form vesicular structures and the deviations from liposomal properties have been studied.
The first project was focused on the influence of the length of the hydrophilic block on the self-assembly in three amphiphilic triblock copolymers with the chemical structure, poly(ethylene glycol) – poly(dimethylsiloxane) - poly(ethylene glycol) (PEG – PDMS – PEG). With increasing the length of the PEG block, each copolymer self-assembled into different structures: micelles, vesicles (polymersomes) and crescent shaped particles.
The focus of the project two, was to analyze the shape deformations and membrane structure changes of the polymersome in response to external forces. Here, the influence of NaCl was studied. The polymersome underwent shape changes from spherical to elongated to multi-vesicular structures, and the overall membrane thickness increased up to 8% as result of osmotic imbalance and the ion-membrane interactions.
In project three, hybrid vesicles resulting from the co-assembly of the lipid, 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and triblock copolymers showed increase in hydrophilic layer thickness of the membrane with decreasing hydrophilic mass fractions of the polymers. The increase in the polymer weight fraction, however, did not affect the membrane thickness or the vesicle size in a significant way.
Initial data on size and shape changes was obtained using dynamic light scattering (DLS) and cryo-transmission electron microscopy (cryo-TEM). Small-angle neutron scattering (SANS) and small-angle X-ray scattering (SAXS) were used for more detailed analysis.
The heterogeneities in size, shape, multi-lamellarity and membrane structure play key roles in vesicular drug delivery. The explorations in this dissertation could assist in understanding and controlling of these parameters.
Perera, Mailange Rasangi, "Manipulating Structure and Membrane Properties of Nano-Scale Model Membrane Systems of Amphiphilic Polymers and Lipids" (2021). LSU Doctoral Dissertations. 5678.
Available for download on Wednesday, October 25, 2028