Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Chemistry

Supervisor

Elizabeth Rachel Gillies

Abstract

The ability to trigger the degradation of polymeric nanoparticles (NPs) by a specific stimulus can provide a method of improved drug targeting and selective release capabilities in vivo. The challenge for most polymeric drug delivery systems remains the necessity for many stimuli events to trigger the release of cargo. Polymeric nanotechnology containing “self-immolative polymers” looks to alleviate the reliance on high concentrations of stimuli by undergoing complete end-to-end depolymerization via a single stimulus-mediated reaction of an end-cap. Herein, NPs were developed using poly(ethyl glyoxylate) (PEtG) blended with poly(d,l-lactic acid) (PLA) to encapsulate a hydrophobic cargo to be released upon stimulus-triggered cleavage of the PEtG end-cap. The PEtG-PLA NPs were formed using an oil-in-water emulsion-evaporation technique. Particles responsive to stimuli including UV light and reducing conditions were prepared and studied. Cleavage of the end-caps of these polymers was accomplished by introducing the relevant stimuli, resulting in a rapid degradation of the particles and subsequent release of cargo. Nile red as a fluorescent probe and the drug celecoxib were encapsulated within the particles and were shown to be released upon introduction of small amounts of the appropriate stimulus. Initial cell culture studies were performed to investigate the behavior of the systems in vitro. This system provides the ability to tune the responsiveness of the NPs by simply changing the PEtG end-cap, making them a great prospect for stimuli-responsive drug delivery vehicles.

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