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Includes abstract. Includes bibliographical references.

Since their initial conceptualization, polymer-drug conjugate nanocarriers have been a mainstay of the drug delivery field. The conjugation of therapeutic agents to polymeric carriers offers several critical advantages including improved drug solubilization, controlled release, and enhanced safety. Accordingly, polymer-drug conjugate nanocarriers are uniquely positioned to remedy some of the limitations of conventional small molecule chemotherapeutics, namely their narrow window of therapeutic efficacy, rapid clearance, and limited tumor exposure. This dissertation describes the design, synthesis, and evaluation of a novel sustained release, biodegradable polymeric nanocarrier as a single administration replacement of multi-dose paclitaxel (PTX) treatment regimens. The synthesis of poly(1,2-glycerol carbonate)-graft-succinic acid-paclitaxel (PGC-PTX) is presented, and its use enables high, controlled PTX loadings. Moreover, the polymer backbone is composed of biocompatible building blocks—glycerol and carbon dioxide. When formulated as nanoparticles (NPs), PGC-PTX NPs exhibit high aqueous PTX concentrations, sub-100 nm diameters, narrow dispersity, prolonged storage stability, and sustained and controlled PTX release kinetics. In murine models of peritoneal carcinomatosis, in which the clinical implementation of multi-dose intraperitoneal (IP) treatment regimens is limited by catheter-related complications, PGC-PTX NPs exhibit improved safety at high doses, tumor localization, and efficacy even after a single IP injection, with comparable therapeutic effect to multi-dose IP PTX treatment regimens. The PGC-PTX NP platform is additionally amenable to optimization via modulation of nanocarrier properties. Specifically, the dual conjugation and physical entrapment of PTX in the NPs harnesses the physicochemical interactions between free and conjugated PTX to achieve unprecedented ultra-high drug loadings as well as facile control of nanomechanical properties and release kinetics. Optimization of these programmable carriers consequently enables the safe delivery of high drug doses as well as sustained therapeutic efficacy. In a murine model of peritoneal carcinomatosis, a single high dose of dual-loaded PGC-PTX nanocarriers affords significantly improved survival compared to weekly, multi-dose PTX treatment. Modulation of nanocarrier properties via the incorporation of poly(lactide-co-glycolide) (PLGA) is additionally explored. Although the integration of PLGA does not significantly alter NP physical properties, the polymer blend nanocarriers exhibit improved in vitro potency relative to PGC-PTX NPs, warranting the continued evaluation of the mechanism by which PLGA modulates nanocarrier efficacy. / 2020-07-02T00:00:00Z

Power generation systems based on solid oxide fuel cells (SOFCs) offer a pathway to a highly efficient and pollution free energy economy. Operation of SOFCs at intermediate temperatures allow the use of metallic interconnects. However, the chromium oxide scale that forms on the metallic interconnect can volatilize and transport and deposit on the cathode, leading to cell performance degradation. The objectives of this dissertation are to understand the role of current density, cathode overpotential, humidity, and cathode composition on Cr-poisoning and suggest mitigation strategies based on this understanding. Conventional (La,Sr)MnO3 (LSM) cathode half-cells have been electrochemically studied to understand the mechanism of Cr-poisoning. The cells have been tested as a function of current density (and thus cathode overpotential), and humidity levels in the oxidant gas. The half-cell measurements have revealed that Cr-poisoning accelerated with cathode overpotential (i.e. current density) and humidity. Microstructural characterization of tested cells found evidence of Cr-rich species at the cathode/ electrolyte interface at high cathode overpotential and humidity. Based on the experimental results, a mechanism of Cr-poisoning has been proposed. With the objective of mitigating Cr-poisoning observed in LSM cathodes, lanthanum nickelate, La2NiO4+δ (LNO) has been studied as an alternative cathode material. Both half-cells and full single SOFCs featuring LNO as the working electrode/cathode, and ferritic stainless steel current collectors have been fabricated. The cells have been tested under the same conditions as the LSM cells. The chromium deposition at the cathode/ electrolyte interface was much reduced for LNO compared to LSM, and the cell performance of cell featuring LNO cathode continually improved with time in contrast to the LSM cell which started to degrade during cathodic current application. Based on the deconvolution of the polarization losses, it was concluded that the higher tolerance of the LNO cathode to Cr-poisoning compared to LSM, can be attributed to maintaining a low cathode activation polarization. The differences in the mechanisms of Cr-poisoning between LSM and LNO has been clarified. A two-pronged strategy combining chromium-tolerant cathodes and interconnect protective coatings is suggested to mitigate long-term performance degradation arising from chromium poisoning.

Phase transformations and chemical interactions occur in many materials systems exposed to elevated temperatures. In this study, materials exposed to high temperatures in three distinctive applications, have been examined. The first application involves the fabrication of semiconductor-core optical fibers for mid-infrared transmission. Such fibers can be used for chemical sensing, threat detection, and bio-imaging. In this study, germanium-core borosilicate glass cladded fibers were fabricated using rod-in-tube drawing. An analytical model for the deformation and heat transfer in the fiber preform during the high temperature fabrication process was developed. The solidification of the germanium core was experimentally studied using a proxy system of melting ice in a tube. The relative roles of conductive and convective heat transfer in determining the melting mechanism was analyzed. The fabricated fibers were characterized by various electron microscopy based techniques to understand impurity diffusion from the cladding to the core, as well as to study the crystalline quality of the Ge core. The second application involves solid oxide membrane (SOM) based electrolytic production of silicon, where the interaction between the ceramic membrane and the molten salt is the key in determining the lifetime of the membrane. The yttria-stabilized zirconia (YSZ) membrane was found to degrade over time due to chemical interactions with the silica-containing molten oxy-fluoride flux. These interactions led to the formation of a yttria depletion layer in the YSZ in contact with the molten salt. A series of flux compositions were designed to systematically test the correlation between flux optical basicity, yttria activity and YSZ membrane degradation. The results provide a guideline for eliminating membrane degradation during the production of silicon using the SOM electrolysis process. The third application involves molten mixtures of lithium chloride and metallic lithium for metal oxide reduction application. These mixtures exhibit anomalous physical properties that lack a comprehensive explanation. In this study, the structures of bulk molten LiCl and LiCl-Li mixtures were investigated using an in-situ high-energy x-ray diffraction (HEXRD) technique. The structure factors and the pair distribution functions (PDF) of LiCl-Li mixtures were compared with those of pure LiCl. The results suggest Li disperses in LiCl as nano-clusters.

This thesis presents a method to detect fibrin formation based on electrical impedance sensing. A polydimethylsiloxane (PDMS) microfluidic device was designed and fabricated to detect fibrin formation in artificial blood samples (solution of fibrinogen, thrombin and CaCl2) by measuring changes in electrical impedance during the process of coagulation. The electrical measurements were performed using a lock-in amplifier. The optical properties of the fibrin in the microfluidic device were observed in an inverted microscope to confirm the clot formation. In the study, the dimensions of the microfluidic devices and the sensing electrodes were optimized to improve the sensitivity and to ensure electrical contact between the electrodes and analyte. An equivalent circuit model was developed to fit the change in the electrical signal of the channel accurately and to determine the optimal measurement frequency. The measured electrical impedances exhibited an expected increase with the blood coagulation. In summary, the technique and the device were shown promising for detecting the blood coagulation process.

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