Multifunctional polymer nanospheres for multimodal imaging and drug delivery following neurotrauma

Research output: ThesisDoctoral Thesis

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Abstract

Protecting intact but vulnerable neurons and glia from damage that occurs secondary to neurotrauma is one of several requirements for successful therapy. Deregulation of calcium ion homeostasis is associated with secondary degeneration and release of excitatory amino acids, initiating cascades that lead to increased mitochondrial production of reactive oxygen species and cell death. Calcium channel blockers such as lomerizine have been shown to prevent calcium influx in vitro and protect against secondary injury effects in vivo, but problems with solubility and rapid excretion limit their usefulness. Nanoparticles can be used as a drug delivery tool to overcome these limitations. In this work, nanoparticles of different types were prepared, with the goal of making a suitable carrier for delivery of lomerizine with provision for imaging and tracking the nanosystem in vitro and in vivo. Combinations of quantum dots, superparamagnetic iron oxide nanoparticles, and fluorescent dyes were investigated as imaging probes, with consideration for their usefulness in biological systems. Initial work investigating multi-pronged imaging tools culminated in the design and synthesis of multifunctional polymer nanospheres that supported both multiple imaging modalities and drug delivery. The effect of these nanospheres on cell viability, and the endocytic routes by which nanospheres are taken up, were investigated using a multimodal approach. Correlated electron microscopy, fluorescence, and relaxometry were used to track endocytosis of the nanospheres in neural cells. Intracellular cytosolic calcium concentrations were measured to show the effective delivery of lomerizine using these designed nanoparticles. The results show that intracellular delivery using labelled nanoparticles may be a feasible approach to deliver sustained doses of lipophilic drugs to central nervous system injury sites.
Original languageEnglish
QualificationDoctor of Philosophy
Publication statusUnpublished - 2012

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