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The main objective of this research was to better understand, predict and control of the periodic precipitation process and to apply such programmed periodic precipitation to the design of a pulsatile delivery system. In the first part of this study, a generalized model taking into account both nucleation, particle growth, and ripening process was refined and solved under various new concentration boundary conditions not previously investigated. The results clearly delineate the key differences between boundary conditions of infinite versus finite supply of inner electrolyte. When the inner electrolyte boundary concentration was allowed to increase exponentially with time, equidistant periodic precipitation was predicted and subsequently confirmed experimentally. In addition, the effects of product solubility and reaction rate constant were also shown to be important in determining the band number and band spacing. In the second part of this study, the effects of gel crosslinking and gel charge density on the periodic precipitation were investigated. The results indicate that by increasing either the gel crosslinking or decreasing the gel charge density will reduce the diffusion rate of the reactants resulting in closely spaced bands. In addition, a new and improved rotating disk method for characterizing polyelectrolyte gels with ion-penetrable soft surfaces has been established by taking into account the effect of surface conductivity which is usually ignored for ion-impenetrable hard surfaces. In the third part of this work, periodic precipitation formed in multi-component systems has been shown to be governed by a heterogeneous nucleation mechanism. Using this approach, periodic precipitation of an insulin mimetic compound VO2+ in gelatin gel, which cannot form alone in a single reaction system, was induced by the periodic precipitation of Mg(OH)2 in a multi-component system. Pulsatile release of VO2+ from the resulting multi-layered structure of VO(OH)2 via a surface erosion mechanism was subsequently demonstrated.

The main objective of this research was to better understand, predict and control of the periodic precipitation process and to apply such programmed periodic precipitation to the design of a pulsatile delivery system. In the first part of this study, a generalized model taking into account both nucleation, particle growth, and ripening process was refined and solved under various new concentration boundary conditions not previously investigated. The results clearly delineate the key differences between boundary conditions of infinite versus finite supply of inner electrolyte. When the inner electrolyte boundary concentration was allowed to increase exponentially with time, equidistant periodic precipitation was predicted and subsequently confirmed experimentally. In addition, the effects of product solubility and reaction rate constant were also shown to be important in determining the band number and band spacing. In the second part of this study, the effects of gel crosslinking and gel charge density on the periodic precipitation were investigated. The results indicate that by increasing either the gel crosslinking or decreasing the gel charge density will reduce the diffusion rate of the reactants resulting in closely spaced bands. In addition, a new and improved rotating disk method for characterizing polyelectrolyte gels with ion-penetrable soft surfaces has been established by taking into account the effect of surface conductivity which is usually ignored for ion-impenetrable hard surfaces. In the third part of this work, periodic precipitation formed in multi-component systems has been shown to be governed by a heterogeneous nucleation mechanism. Using this approach, periodic precipitation of an insulin mimetic compound VO2+ in gelatin gel, which cannot form alone in a single reaction system, was induced by the periodic precipitation of Mg(OH)2 in a multi-component system. Pulsatile release of VO2+ from the resulting multi-layered structure of VO(OH)2 via a surface erosion mechanism was subsequently demonstrated.

Application of neural prostheses in today's medicine successfully helps patients to increase their activities of daily life and participate in social activities again. These implantable microsystems provide an interface to the nervous system, giving cellular resolution to physiological processes unattainable today with non-invasive methods. The latest developments in genetic engineering, nanotechnologies and materials science have paved the way for these complex systems to interface the human nervous system. The ideal system for neural signal recording would be a fully implantable device which is capable of amplifying the neural signals and transmitting them to the outside world while sustaining a long-term and accurate performance, therefore different sciences from neurosciences, biology, electrical engineering and computer science have to interact and discuss the synergies to develop a practical system which can be used in daily medicine practice. This work investigates the main building blocks necessary to improve the quality of acquired signal from the micro-electronics and MEMS perspectives. While all of these components will be ultimately embedded in a fully implantable recording probe, each of them addresses and deals with a specific obstacle in the neural signal recording path. Specifically we present a low-voltage low-noise low-power CMOS amplifier particularly designed for neural recording applications. This is done by surveying a number of designs and evaluating each design against the requirements for a neural recording system such as power dissipation and noise, and then choosing the most suitable topology for design and implementation of a fully implantable system. In addition a surface modification method is investigated to improve the sacrificial properties and biocompatibility of probe in order to extend the implant life and enhance the signal quality.

The first objective of this thesis was to assess the feasibility of designing a “smart” degradable polymer that can release anti-inflammatory drugs in response to inflammatory-related enzymes. The drug polymer was synthesized using diisocyanates, poly(caprolactone)diols, and oxaceprol (OC) biomonomers. Biodegradation studies demonstrated that the trimethylhexamethylene diisocyanate-based drug polymer responded to an inflammatory enzyme to release more OC, while a 1, 12-diisocyanatododecane analog demonstrated minimal drug release. The drug delivery response was believed to be a direct function of the molecular structure and distribution of the hard segment. The second objective of this thesis was to elucidate the anti-inflammatory mechanisms of OC by investigating its effects on cytokine-induced monocytic-cells adhesion in human umbilical vein endothelial cells (HUVECs) in vitro. Results showed that OC had no direct effect on the monocyte-endothelium adhesion, suggesting that OC may mediate inflammation by mechanisms other than those suggested by the literature.

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My MSc project aims at developing pH-responsive molecular tweezers for drug delivery applications. The project began with the synthesis of our 2nd generation tweezer, whose main objective was to improve our previous model, 1st generation tweezer, which contained a pH-responsive triad spacer and two naphthalene walls known to interact with hydrophobic drugs such as Mitoxantrone®. The naphthalene interaction sites were successfully modified to contain oligoethylene glycol chains to improve their water-solubility, in anticipation for more accurate measurements of pKa and binding constants in aqueous media. However, all attempts to convert such naphthalene derivatives into their corresponding boronic acid or ester through standard protocols (halogen-lithium exchange, palladium catalyzed borylation) failed. Without the required boronic acid/ester, the final Suzuki-Miyaura coupling with the di-bromo triad spacer was not achieved. Synthesis of the 3rd generation tweezer, which was modified to contain theophylline as the new interaction sites, was then attempted. The half-tweezer was successfully synthesized via copper (II) catalyzed coupling of theophylline with the 5-bromo-4-methoxyphenyl boronic acid. However, all attempts to convert it into the required boronic acid/ ester for the final Suzuki- Miyaura coupling reaction with 2,6-dibromopyridine failed. We then focused our attention on the conversion of the triad spacer into its corresponding diboronic acid. The synthesis of the triad diboronic acid was a success, however, the final copper (II) catalyzed reaction with theophylline to form the tweezer only yielded the mono-coupled product. Lastly, our 4th generation tweezer was engineered to avoid the synthetic difficulties encountered in the boronic acid/ ester synthesis stage. Using the commercially available 5-formyl-2-methoxyphenylboronic acid and o-phenylenediamine, we successfully synthesized a benzimidazole-derived “half tweezer” through ring condensation reaction. Alkylation of this half-tweezer was also successfully achieved, although purification of the alkylated product was not optimized. Using this crude product, we carried out the final tweezer reaction via Suzuki- Miyaura coupling with 2,6-dibromopyridine under microwave irradiation. 1H NMR results show formation of new species that is believed to be the 4th generation tweezer (although the presence of impurities made integration of the signals unreliable). Much work is needed in the purification of the alkylated half tweezer boronic acid in order to avoid complicated mixtures in the final tweezer reaction. / Thesis (Master, Chemistry) -- Queen's University, 2011-10-06 00:29:04.248

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