Electronic Thesis and Dissertation Repository

Degree

Master of Engineering Science

Program

Chemical and Biochemical Engineering

Supervisor

Dr. Elizabeth R. Gillies

Abstract

The objective of this research was to develop polymeric nanoparticles (NPs) having improved drug release properties for drug delivery. Poly(ester amide)s (PEAs) are promising biodegradable polymers. PEA NPs were prepared via emulsification-evaporation and salting-out methods and optimized through by varying different processing parameters. Polymer-model drug conjugates based on PEAs containing L-aspartic acid and rhodamine B were synthesized and used for NP preparation. Release behavior was studied and compared to a control system with physically encapsulated rhodamine B. It was shown that the release of rhodamine B from the covalent system did not show the burst effect and exhibited a slower and more sustained profile. A novel PEA-floxuridine conjugate was also prepared and used to synthesize NPs. These NPs exhibited a small burst effect followed by slow drug release. To provide a new stimulus-responsive release mechanism, NPs based on a UV triggerable self-immolative poly(ethyl glyoxylate) PEtG were prepared. PEtG/poly(lactic acid) (PLA) blend NPs were prepared for site-specific and time-controlled drug delivery. PLA NPs were first synthesized by the emulsion-evaporation method and optimized through different experimental conditions. PEtG/PLA NPs were then prepared using the optimized conditions. In this study, letrazole was used as a model drug. These letrazole loaded NPs had a low Z-average diameter of less than 100 nm and high encapsulation efficiency. Increasing burst release was observed with increasing PLA content. Thermal characterization of PEtG/PLA NPs showed phase separation of the two polymers in the NPs. Although the UV irradiated PEtG NPs showed depolymerization upon UV irradiation, letrazole release was not accelerated. The reasons for this lack of triggered release require more investigation and optimization.

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