Master of Science
Gillies, Elizabeth R.
Stimuli-responsive hydrogels have attracted significant research interest as they exhibit triggerable drug release or changes in mechanical properties. Hydrogels containing dendrimers have also been targeted as their multiple functional groups provide enhanced crosslinking or chemical conjugation. Self-immolative dendrimers (SIDs) fragment in response to a stimulus event, but they have not been explored for the preparation of stimuli-responsive hydrogels. This thesis reports the preparation of hydrogels from a 4-arm poly(ethylene glycol) polymer and SIDs composed of a photosensitive o-nitrobenzyl carbonate core. The gel content and equilibrium water content were examined as a function of the hydrogel formulation. Hydrogel degradation was demonstrated using 1H NMR spectroscopy and measurements of the mechanical properties before and after degradation. The loading and release of the drug celecoxib from the hydrogels was also investigated. This work introduces a new implantable stimuli-responsive dendritic hydrogel platform that can potentially be used for the delivery of celecoxib or cell encapsulation and release.
Summary for Lay Audience
Certain molecules with tree-like morphologies have attracted a lot of interest due to their structural precision and functional diversity. Such characteristics afford them various applications in drug delivery, catalysis, sensors, and agriculture. This group of molecules has recently been extended to include a new class of materials, which are comprised of three components: (i) central core (ii) interior branches and (iii) peripheral functional groups from which molecules are released. The novel species fragment in a domino-like fashion in response to a trigger event, such as UV light irradiation, at the core. However, their incorporation into hydrogels has not yet been explored. Hydrogels are of significant interest for biomedical applications due to their high water content, which resembles that of tissues. They have been investigated for both cell and drug delivery. This thesis describes the synthesis of hydrogels that contain photosensitive tree-shaped moieties. Upon exposure to UV light, the fragmentation of the networks was assessed. The scaffolds were made to ensure the degradation products were not toxic to the human body. Also, the durability of the scaffolds in the presence and absence of UV light was examined. Finally, the hydrogels were loaded with drug molecules to investigate the networks’ drug release behaviour with and without irradiation. Overall, the materials produced in this thesis are proof-of-concept for the development of future biomaterials for cell and drug delivery.
Gill, Karanpreet, "Self-Immolative Dendritic Hydrogels" (2021). Electronic Thesis and Dissertation Repository. 7902.
Available for download on Friday, December 31, 2021