All ETDs from UAB

Advisory Committee Chair

Eugenia Kharlampieva

Advisory Committee Members

Ganesh Halade

Sergey Vyazovkin

Eddy Yang

Jun Zhang

Document Type


Date of Award


Degree Name by School

Doctor of Philosophy (PhD) College of Arts and Sciences


Synthetic nanovesicles, known as liposomes, are assembled from synthetic lipids as encapsulation devices for delivery of small molecules and are now a key component of COVID-19 mRNA vaccines. Due to their similarity to a cell membrane, liposomes also find use in anticancer treatment to reduce toxic side effects of chemotherapy. However, synthetic liposomes may require a multi-step synthesis, and very often show poor physical and chemical stability. In contrast, polymeric vesicles (polymersomes) assembled from synthetic polymers can boast much better mechanical and chemical stabilities and provide stimuli responsiveness that can enhance targeted drug delivery and provide drug release on-demand. Polymersomes responsive to external stimuli such as temperature and low pH can be utilized to specifically release anticancer therapeutics into the tumor environment that has lower than physiological pH (pH < 7) and an elevated temperature (40-42 °C) due to tumor high glycolysis rate and fast proliferation. Along with synthesis of rationalized polymer systems, the structural characterization of polymersomes assembled from those polymers is necessary in the presence or absence of the external stimuli to understand the structural changes responsible for triggered cargo release from the polymeric vesicles. For this dissertation, nanoprecipitation, thin film rehydration and microfluidc mixing of novel synthesized ABA-type triblock copolymers are utilized to produce nano- and micrometer-sized polymeric vesicles that demonstrate temperature- and pH-responsive structural changes, and stimuli-triggered release of functional molecules. Three main parts are described: 1. The synthesis of three ABA-type triblock copolymers with varied chain lengths and hydrophilic ratios. 2. Assembly of nano- and micrometer-vesicles from those polymers and their nanoscale structural characterization. 3. Stimuli-triggered responses of the polymersomes. These temperature- and pH-responsive polymeric vesicles have potential as a new platform for design of advanced polymeric delivery systems, while the discovered mechanisms of the structural changes of the vesicles will provide design guidance for development of advanced ‘intelligent’ polymeric vesicles. Chapter 2 explored the methodology of SANS measurements for vesicles. Contrast matching methods allowed for enhancing features of the vesicles, the form-factors and structure factor of the vesicles and the derivation of vesicular structures from scattering was also discussed. Different methods for data fitting and reduction were discussed for in-situ characterization of the membrane thickness, the inner radius and the size of particles for hydrated vesicles. Chapter 3 described the synthesis of a library of PVCL-PDMS-PVCL triblock copolymers and the effects of molecular weight, polymer block weight ratios, and temperature on the structure of these polymersomes using electron microscopy, DLS, small-angle neutron scattering (SANS), and all-atom molecular dynamic methods. Near-atomic analysis of the vesicle structure revealed that these polymersomes collapse into smaller vesicles with thinner shells above the LCST, but the extent of each transformation is highly dependent on the hydrophilic-to-hydrophobic ratio f. The exploration of these mechanisms and our findings have brought the understanding of the temperature-induced changes in polymersome structures and the responsive behavior resulting in controlled stimuli-triggered release of functional molecules. Chapter 4 explored a simple approach for synthesis of temperature-responsive GUVs from PVCL15-PDMS65-PVCL15 triblock copolymer and non-temperature responsive small and giant vesicles from novel PVPON15-PDMS65-PVPON15 and PVPON6-PDMS30-PVPON6 triblock copolymers using microfluidic mixing at 25 °C. Stability of temperature-responsive PVCL15-PDMS65-PVCL15 GUVs and PVPON15-PDMS65-PVPON15 GUVs at 25 and at 42℃ was explored. The effect of physical crosslinking of PVCL15-PDMS65-PVCL15 GUVs’ PVCL corona with polyphenol on stability and degradability of GUVs were also investigated. The developed GUVs have potential in theranostic drug delivery as substitutes for polymer microcapsules and lipid microbubbles as well as for stimuli-triggered sensing, protection, and rapid response in an aqueous environment.



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