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

This thesis includes two parts related to hydrogels as therapeutically useful constructs: a biomimetic hydrogel carrying stem cells for bone regeneration and an acid-sensitive hydrogel carrying drugs for cancer therapy. In tissue engineering, one of the biggest difficulties is the control of stem cell fate on scaffolds. A biodegradable and cell attachable cross-linker was synthesized by one-step Michael additional reaction, and was used to fabricate a novel hydrogel to control the stem cell fate. For anti-cancer therapy, releasing drug on tumor cells or organs while having low effects on health cells under physiological conditions is a critical requirement. Two nature polymers are modified to achieve loading anti-cancer drug while forming hydrogels which can selectively release the drug in tumor environment by acid-sensitive linkages.

A scalable method for the synthesis of polyethylene terephthalamide microcapsules grafted with polyacrylic acid to enable pH responsiveness has been developed. Microcapsules were produced by interfacial polymerisation of an oil-in-water emulsion in a 2 L batch reactor and subsequently circulated through an external loop reactor for UV irradiative surface grafting. Ungrafted microcapsule samples yielded 1.0 - 1.2 g desiccated capsules per experiment. Initial production trials were subject to severe agglomeration, observed during dialysis of the microcapsules with 30 % (v/v) ethanol solution. Lowering of the terephthaloyl dichloride monomer concentration, to 0.2 mol L⁻¹ in the chloroform / cyclohexane (3 : 1) organic solution, alleviated this unwanted agglomeration. Laser diffraction particle size analysis revealed microcapsules were produced with a 51 µm average diameter. A purpose built external loop irradiation reactor was used to facilitate graft polymerisation of acrylic acid on the microcapsules, using 254 nm UV light at 19 mW cm⁻². Characterisation of the external loop flow regime showed a mild deviation from ideal plug flow, with a vessel dispersion number of 0.014 and a Reynolds number of 1310. Confirmation of monomer polymerisation was ascertained by back titration and Fourier transform infrared spectroscopy. No distinction between homopolymer and grafted polyacrylic acid could be made by these characterisation methods. A Taguchi analysis on variables influencing grafting revealed high temperature to contribute most significantly to graft yield, followed by a long irradiation period. The development of a packed column pulse response method for testing pH response showed a high repeatability. However, release profile testing of a microcapsule slurry with an observed graft yield of 1.13 mmol g⁻¹ did not provide a definitive pH-based release of mPEG 5000 or PEGylated TAMRA dye. Determination of acrylic acid polymerisation kinetics following UV irradiation of the microcapsules is required for future optimisation of a functional graft yield.

This thesis includes two parts related to hydrogels as therapeutically useful constructs: a biomimetic hydrogel carrying stem cells for bone regeneration and an acid-sensitive hydrogel carrying drugs for cancer therapy. In tissue engineering, one of the biggest difficulties is the control of stem cell fate on scaffolds. A biodegradable and cell attachable cross-linker was synthesized by one-step Michael additional reaction, and was used to fabricate a novel hydrogel to control the stem cell fate. For anti-cancer therapy, releasing drug on tumor cells or organs while having low effects on health cells under physiological conditions is a critical requirement. Two nature polymers are modified to achieve loading anti-cancer drug while forming hydrogels which can selectively release the drug in tumor environment by acid-sensitive linkages.

This thesis focuses on the design, fabrication and characterization of polymeric smart structures that are able to alter their geometry and thus their properties upon the application of external stimuli in a reversible and controllable manner. Two different responsive structures are studied that both contain poly dimethyl-siloxane (PDMS) and differ in the design, geometry, and actuation mechanism. The first structure is a surface decorated by a square array of posts (cilia) made of PDMS reinforced with magnetic particles and is actuated magnetically. The structures are meant to mimic cilia, a hair-like structure found in nature. The physical parameters necessary for the magnetic response of the cilia including physical dimensions and filler concentration are investigated. In addition, the elastic modulus of the composites is measured and the microstructure is examined in order to determine the dispersion and homogeneity of the composites. The second structure is a planar hetero-structure consisting of a PDMS substrate and a nanoporous (NP) metal foam film which is actuated thermally or chemically by tuning the generation and release of residual stresses at the NP metal foam/PDMS interface. The effect of strain, applied to the PDMS substrate prior to the deposition of the NP metal foam and the effect of the PDMS and NP metal foam thicknesses on the shape/size of the planer hetero-structure after the actuation is investigated.

The objective of this thesis is to investigate well-defined cross-linked particles synthesized via the reversible addition fragmentation chain transfer (RAFT) process that can be used for drug delivery. To achieve this aim, a wide range of cross-linked micelle systems have been synthesized and intensively investigated. Various biocompatible monomers were employed, including poly (ethylene glycol) methyl ether methacrylate, 2-hydroxyl ethyl acrylate, functionalized glucosamine and nucleotides containing monomers. Different cross-linked structures were used, for example, core-cross-linked, nexus-cross-linked and shell-cross-linked micelles. Diverse stimuli-responsive particles were used, such as pH-sensitive, thermo-sensitive and thiol-sensitive cross-linked systems. Evidences of the successful synthesis of all the resulting cross-linked products are given. They displayed better properties, as drug carriers, than non-cross-linked micelles. A thermo-responsive seven-arm star glycopolymer, synthesized via the RAFT process, was also investigated.

This master thesis shows which qualities should modern website have and which technologies should be used to achieve them. The thesis should mainly point out, what are the unwritten requirements of the websites nowadays and what the latest trends in this field are. It also mentions which components can be used when creating a website. In the theoretical part there is described the historical development of technical background of the web technology. The following section analyses current web platform development phase and all the new possibilities that are there for the developers and users both. The next part of the thesis shows what the requirements when creating modern websites are and which technologies can be used to fulfil them. In the practical part I am concentrating on developing a new website (from the design to the development, including testing and optimization) while using all of the modern technologies and trends in this field.

Following the call of recent authors for an improved process-oriented model of entrepreneurship, this exploratory research study sets out to understand the process of entrepreneurship, or “entrepreneuring”. It uses perspectives from the process-oriented view of reality, social constructionism and the complexity sciences. The aim of this study was to construct new questions, using the theoretical lens afforded by these perspectives, which would fuel further research toward developing a process-oriented model of entrepreneurship ‒ or point out the intractability of such a problem. Eleven individuals, who were considered to be early-stage entrepreneurs, were selected for qualitative interviews. A narrative analysis of these interviews was performed which showed, within the context of the process of entrepreneuring, that the emergent themes could be understood from the alternative theoretical paradigms covered in the literature. Several important questions for future research emerged, alongside the understanding that an alternative to the mechanistic/systemic perspective is to be sought, and that the process of entrepreneuring might be better understood within the broader context of power and social influence dynamics. / Dissertation (MBA)--University of Pretoria, 2012. / Gordon Institute of Business Science (GIBS) / unrestricted

Liposomes are promising drug delivery vesicles due to their biodegradibility, large volume and biocompatibility towards both hydrophilic and hydrophobic drugs. They suffer, however, from poor stability which limits their use in controlled delivery applications. Herein, a novel method was devised for modification of liposomes with small molecules, polymers or nanoparticles to afford stimuli responsive systems that release on demand and stay relatively stable in the absence of the trigger.. This dissertation discusses thermosensitive, pH sensitive, light sensitive and magnetically triggered liposomes that have been prepared for controlled drug delivery application. RAFT polymerization was utilized for the preparation of thermosensitive liposomes (Cholesterol-PNIPAm) and acid-labile liposomes (DOPE-PAA). With low Mw Cholesterol-PNIPAm, the thermosensitive liposomes proved to be effective for controlled release and decreased the cytotoxicity of PNIPAm by eliciting the polymer doses. By crosslinking the DOPE-PAA on liposome surface with acid-labile diamine linkers, DOPE-PAA liposomes were verified to be sensitive at low pH. The effects of polymer structures (linear or hyperbranched) have also been studied for the stability and release properties of liposomes. Finally, a dual-responsive Au@SPIO embedded liposome hybrid (ALHs) was prepared with light-induced “on-and-off” function by photo-thermal process (visible light) and instant release properties triggered by alternating magnetic field, respectively. The ALH system would be further applied into the cellular imaging field as MRI contrast agent.

Federal government agency reports have documented concerns regarding the use of school discipline and suspension indicating that Black students are referred for discipline and/or suspended at a higher rate than students of other ethnicities. Available data from the local school district involved in this study reflected similar troubling patterns of discipline referral and suspension. The purpose of this study was to determine if variables such as ethnicity, socioeconomic status, and gender predict the likelihood of receiving discipline referrals or being suspended at an affiliated charter high school in the local school district. Guided by Bandura's social learning theory, this correlational explanatory quantitative study examined archival school discipline data for 1,570 students who received at least one discipline referral or suspension during the 2013-2014 school year at the local high school. Binomial logistic regression results showed that Black male students from low socioeconomic backgrounds were significantly more likely to be suspended compared to other ethnicities. Negative binomial regression analysis indicated students who were Black, male, and were from low socioeconomic backgrounds were at significantly greater risk of receiving a referral than other ethnicities. A professional development training was designed to provide school personnel with culturally-responsive, preventative discipline strategies that meet the needs of all students including those who are at highest risk for punitive discipline and suspension. By equipping school personnel in this and similar school communities with culturally-responsive discipline strategies aimed at meeting the needs of all students, diverse student populations are likely to experience greatly needed positive social change exemplified by improved social, behavioral, and academic outcomes.