Cholesterol conjugated polymers as therapeutic delivery vehicles : correlation between physicochemical and biological properties

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Copyright: Sevimli, Sema
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Abstract
The use of nano-sized synthetic polymers, comprised of therapeutic entities like drugs, genes or peptides, in clinical development has established polymer therapeutics as a credible option for nanomedicine. These nanoscale delivery vehicles offer significant advantages as they enhance therapeutic efficiency by protecting genes against degradation, improving solubility of hydrophobic drugs, reducing potential immunogenicity, and/or releasing therapeutics in a sustained or stimuli-triggered manner. Enhancement of cytoplasmic delivery of polymer therapeutics can be achieved by using lipid structures, such as cholesterol, that promote membrane tethering and endocytosis into endosomes by interacting with the cell membrane. Considering this, a library of well-defined cholesterol-derived ionic copolymers composed of both biological and synthetic moieties with diverse surface charges were generated as potential smart therapeutic delivery systems. The physicochemical properties and functions of the bio-hybrid constructs were carefully tuned by altering the cholesterol units in the copolymer composition. The membrane destabilisation activity, self-assembly and stimuli responsive properties of the ionic copolymers were investigated using numerous techniques. The cellular internalisation and delivery profiles of the polymer-therapeutic complexes, prepared with either genes or chemotherapeutic drugs, were assessed in both carcinoma and healthy cell lines. Finally, transfection and imaging assays were employed to illuminate the copolymer structure-efficacy relationship for each therapeutic design.
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Author(s)
Sevimli, Sema
Supervisor(s)
Davis, Thomas P.
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Publication Year
2013
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Thesis
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PhD Doctorate
UNSW Faculty
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