The Incorporation of Phosphorus into Polymer Networks for Drug Encapsulation and Release
Abstract
This thesis focuses on the incorporation of phosphonium salts into polymer networks for uses in drug delivery and antibacterial coatings. Compared to their ammonium analogues, which have been extensively investigated, phosphonium salts were of interest due to their different chemical properties and their higher chemical and thermal stabilities. The thesis describes the development of covalently crosslinked hydrogels, ionically crosslinked hydrogels and thin film materials to be utilized in the aforementioned applications.
Covalently crosslinked hydrogels were developed with the targeted application of drug delivery. The hydrogels were created by curing formulations with ultra-violet light. Then, anionic drug molecules were loaded, which would be contained in the hydrogels by electrostatic interactions. Release of the drug molecules was performed over 7 days in buffer and could be tuned based on the structure of the phosphonium salt and the pH and ionic strength of the release media. To lengthen the time to release these drugs, an alternative approach utilizing ionically crosslinked hydrogels was employed next. Four phosphonium polymers were produced and mixed with sodium hyaluronate to create ionic networks and their mechanical and rheological properties were studied to determine the differences in network properties. The ionic hydrogels showed sustained release of drug molecules over a period of 60 days and were also able to self-heal after damage in the presence of the release medium. Another ionic network was also synthesized using analogous ammonium and phosphonium polymers with alginate to compare network properties, release rates and self-healing abilities between ammonium and phosphonium polymers. This study proved that changing the polyanion does affect network properties and in this case, increased the release rate of drugs. It was also discovered that in analogous networks the identity of the cation (N or P) did not affect the release rate, but rather the substituents around the atoms did have an effect. Phosphonium salts were then incorporated onto self-immolative polymers for use as antibacterials. These polymers were then further functionalized with polymerizable allyl moieties to allow for crosslinking and thin film formation with the intended use of antibacterial surfaces that could degrade on command.