Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Chemistry

Supervisor

Ragogna, Paul J.

2nd Supervisor

Gillies, Elizabeth R.

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.

Summary for Lay Audience

Modern medicine relies on the efficient delivery of drugs to treat infections and diseases. Ideally, these drugs should be administered at the exact concentration needed, target the affected area only and not harm healthy cells or tissues. Unfortunately, the delivery of drugs into the body is not so easy, as the rate of release, the area of release and stability of the drug need to be accounted for. To mediate these issues, drug delivery systems have been developed in hopes that relevant drugs can be administered in a safe and effective way. The need for these systems has increased dramatically over the years as new drugs, with different properties are continuously being developed. One of the most popular types of drug delivery system involves the use of hydrogels, which are materials that absorb large amounts of water. The high-water content can give them physical similarities to tissues which often makes them well tolerated in the body and gives them the ability to easily encapsulate drugs. There are many different ways to encapsulate drugs and release them in a controlled manner. For example, negatively charged drugs can be bound to positively charged polymers because opposite charges attract. In this thesis, phosphonium salts will be incorporated into hydrogels as the positive charges that can entrap negatively charged drugs. The drugs will then be released in media that has a similar salt concentration to the human body to mimic physiological conditions and a variety of different studies will be completed to compare hydrogel structure and drug release rate.

Positively charged phosphonium species also have inherent antibacterial properties as they can interact with negatively charged membranes of bacteria to cause cell death. This allows phosphonium salts to be incorporated into many different materials to help combat the spread of bacteria. For example, phosphonium containing coatings can be designed and applied to common surfaces such as door handles and tables to kill bacteria on contact, but over time these antibacterial coatings kill and accumulate dead bacteria and become inert. To deal with this issue, this thesis will also investigate phosphonium containing degradable antibacterial coatings. These coatings will be created to kill bacteria, but also be able to degrade upon command after high bacteria accumulation.

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