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This thesis is a creative work of fiction in the form of one novella and four short stories. The collection is a work of humour and entertainment. “The Coin Collective” delves into the cut-throat world of cosplay, “The Dead of Waynesboro” follows Declan Mortel as her tries to create the ultimate zombie movie in true gothic fashion, “220 Torren Mill Road” is an epistolary horror story about a whack-job mother and her game-addicted son, “Dragon’s Lair Comics & Collectables” is set during a Magic the Gathering tournament and questions ‘what makes a monster?,’ and Chemical Connection explores drug and raver culture through an eclectic variety of characters. I hope the collection will speak to an entire generation of self-described and closet geeks. For those without intimate knowledge of the material, I endeavoured to exhibit, even expose, aspects of specific subcultures, shedding light on the basement dwellers who inhabit them.

Microcrystalline cellulose (MCC) is the most commonly used excipient in the manufacture of spherical particles or beads by extrusion spheronisation. However, the use of MCC in beads has its limitations such as prolonged release of drugs due to lack of disintegration. The aim of this study was to determine if Aloe vera and Aloe marlothii leaf materials can be used as excipients in the production of beads prepared by extrusion spheronisation. A 23 full factorial design was employed for optimisation and to explore the effects of the concentration of MCC, polyvinylpyrrolidone and aloe materials on the sphericity and release rate of ketoprofen. Scanning electron microscopy revealed more porous beads when aloe materials were included in the bead formulations compared to the formulation with MMC alone. The bead formulations containing aloe materials exhibited faster drug release compared to that of the formulation containing MCC alone. Dissolution data of the optimised formulations were analysed in terms of mean dissolution time (MDT) as well as fit factors (f1 and f2). The optimised bead formulations had dissolution profiles comparable to that of the formulation containing MCC alone at pH 1.2 and 4.5 (f2 values > 70), but less comparable to the reference at pH 6.8 (50 < f2< 65) due to faster drug release. Aloe vera and Aloe marlothii leaf materials can be used successfully together with MCC in the production of beads by extrusion spheronisation. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.

Microcrystalline cellulose (MCC) is the most commonly used excipient in the manufacture of spherical particles or beads by extrusion spheronisation. However, the use of MCC in beads has its limitations such as prolonged release of drugs due to lack of disintegration. The aim of this study was to determine if Aloe vera and Aloe marlothii leaf materials can be used as excipients in the production of beads prepared by extrusion spheronisation. A 23 full factorial design was employed for optimisation and to explore the effects of the concentration of MCC, polyvinylpyrrolidone and aloe materials on the sphericity and release rate of ketoprofen. Scanning electron microscopy revealed more porous beads when aloe materials were included in the bead formulations compared to the formulation with MMC alone. The bead formulations containing aloe materials exhibited faster drug release compared to that of the formulation containing MCC alone. Dissolution data of the optimised formulations were analysed in terms of mean dissolution time (MDT) as well as fit factors (f1 and f2). The optimised bead formulations had dissolution profiles comparable to that of the formulation containing MCC alone at pH 1.2 and 4.5 (f2 values > 70), but less comparable to the reference at pH 6.8 (50 < f2< 65) due to faster drug release. Aloe vera and Aloe marlothii leaf materials can be used successfully together with MCC in the production of beads by extrusion spheronisation. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.

Controlled release formulations offer many advantages over conventional dosage forms. These include reduced plasma fluctuations and improved patient comp1i:nce. Complex controlled release formulations such as those with enteric release properties, often require additional steps in the production phase. The costs and economic impact associated with these complex controlled release dosage formulations often outweigh the immediate benefits. Thus the development of an economic method to produce controlled release particles is of great importance especially in third world countries. In controlled release formulations, the drug is generally dispersed throughout a polymer matrix. The rate of drug release is often determined by the viscosity or complexity of the polymer matrix through which the drug needs to diffuse in order to be released. With enteric release the polymer coating, insoluble in an acidic environment is often applied in the final phase of production. Chitosan is a versatile polymer of natural origin with many favourable characteristics. These include its safety, biocompatibility, and biodegradability. Simple methods can be applied and modified to produce controlled release particles form chitosan. The effect of modern controlled release polymers such as Aqoat AS-HF, Eudragit SlOO and Kollidon SR was investigated. Chitosan beads and chitosan-polymer beads, as well as chitosan granules and chitosan-polymer granules, were prepared and investigated as possible controlled release formulations. Ketoprofen was chosen as the model drug. Chitosan beads and chitosan-polymer beads were prepared by inotropic gelation in tripolyphosphate. Chitosan granules and chitosan-polymer matrix granules were prepared by binding chitosan with an acetic acid solution as a granulating system. The beads and granules appeared differed in appearance as well as in the results obtained from various experiments. Granules prepared in the study did not appear to be effective with regards to enteric and controlled release. Beads prepared form Kollidon SR appeared to be effective with regards to enteric and controlled release, with Kollidon 1% and 5% w/v chitosan beads achieving good drug loading of up to 73.13% and releasing less than 15 % of the total drug content in 0.1 M HCI after 60 minutes. Drug release continued steadily for up to 360 minutes in pH 7.2. It was concluded that Kollidon SR loaded chitosan beads nay be a viable controlled release dosage form with enteric release properties, and that future experiments, possibly with lower polymer concentrations, are worthwhile / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2006.

Controlled release systems aim at achieving a predictable and reproducible drug release profile over a desired time period. These controlled release formulations offer many advantages over conventional dosage forms. These advantages include: reduced dosing intervals, constant drug levels in the blood, increased patient compliance and decreased adverse effects. Complex controlled release formulations such as those with sustained release properties, often require additional steps during the production phase. The cost and economic impact associated with these complex controlled release dosage formulations often outweigh the short term benefits. Thus the development of an economic method to produce controlled release particles is of great importance especially in third world countries. In controlled release formulations the drug is often equally dispersed throughout a polymer matrix. In the presence of a thermodynamically compatible solvent, swelling occurs and the polymer releases its content to the surrounding medium. The rate of drug release can be controlled by interfering with the amount of swelling and rate of diffusion by manipulating the viscosity of the polymer matrix. Chitosan is an ideal candidate for controlled drug delivery through matrix release systems. It is a biodegradable polymer with absorption-enhancing properties. Cross-linking chitosan with different cross-linking agents allow the preparation of beads. Beads are frequently used in controlled release dosage forms as they are very flexible in dosage form development and show various advantages over single unit dosage forms. Because beads disperse freely in the gastrointestinal tract they maximize drug absorption, reduce fluctuation in peak plasma, and minimize potential side effects without lowering drug bio-availability. Chitosan beads and excipient containing chitosan beads were prepared and investigated as possible controlled release formulations. Pyrazinamide was chosen as the model drug. Chitosan beads and excipient containing chitosan beads were prepared by ionotropic gelation in tripolyphosphate. In this study chitosan/pyrazinamide beads containing pharmaceutical excipients (Ascorbic acid, Explotab and Ac-Di-Sol) were produced. The excipients were added individually and in combinations to the chitosadpyrazinamide dispersion and the beads were characterized on the basis of their morphology, solubility, fiability, drug loading capacity and swelling behaviour, as well as drug release (dissolution properties). The drug loading of the pyrazinarnide loaded chitosan beads, was 52.26 % 0.57%. It was noted that the inclusion of excipients in the beads resulted in an increase in drug loading with the combination of Ascorbic acid and Ac-Di-Sol giving the highest drug loading of 67.09 ± 0.22%. It was expected that the addition of the pharmaceutical excipients would lead to a sustained release of pyrazinamide. Dissolutions studies, however, revealed a burst release in both phosphate buffer solution (PBS) pH 5.60 and 7.40 over the first 15 minutes and the curve reached a plateau after 30 minutes. Thus, apparently the inclusion of the pharmaceutical excipients did not contribute to a sustained release of pyrazinamide over the tested period of six hours. In future studies the dissolution time can possibly be extended to a period of 24 hours. It might be possible for the remaining drug (approximately 40%) in the beads to be released over the extended period. Other polymers can also be investigated to control the release of pyrazinamide. Further studies are, however, necessary to investigate this possibility in the future. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

Proteins play important roles in most cellular functions, such as, replication, transcription regulation, signal transduction, for catalyzing chemical reaction, etc. Technologies developed to identify proteins rely either on observing their own properties such as charge, size, mass to charge ratio or sequence composition; or on using affinity reagents that recognize specific protein targets. Immunoassays utilizing functionalized affinity reagents are powerful for targeted proteomics. Among them, DNA-assisted immunoassays in which affinity reagents are labeled with DNA molecules, offer some unique advantages. In this thesis, I will present works to improve current DNA-assisted immunoassays such as proximity ligation assays (PLA), as well as to take advantage of DNA reactions to adress other problems. In paper I, a new solid support (MBC-Ts) was functionalized with antibodies and used in the solid-phase PLA for detection of VEGF. The assay using MBC-Ts was compared among the commercially available solid supports in different matrices and it was shown to exhibit enhanced limit of detection in complex matrices. In paper II, a two-step protocol was described to prepare high-quality probes used in homogeneous and in situ PLA by purifying DNA-labeled affinity reagents from unconjugated affinity reagents and excess oligonucleotides. In paper III, PLA was applied on a capillary western blotting instrument so that both the sensitivity and specificity of the original assay were improved. In paper IV, a new method was introduced to profile protein components in individual protein complexes by DNA-barcoded antibodies. This method has been used to profile protein complexes such as surface proteins on individual secreted vesicles.

Th.--Archéol. / Bibliogr. p. 235-246.

Health Care Associated Infections (HCAIs) are a concern especially in regards to antibiotic resistance and effective treatments. Staphylococcus aureus is often the main focus for eradication and prevention procedures, however, other bacterial species are also problematic. These include Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Staphylococcus epidermidis amongst others. Chronic infections caused by these bacteria are often biofilm related, and include dental caries, otitis media, osteomyelitis, burns & chronic wounds, and device related & prosthetic joint infections. Prosthetic joints and indwelling devices, such as catheters, are a prime environment on which biofilms can develop. This thesis aims to look at biofilms, investigating how they are established, the development of resistance against individual antibiotics and the antibiotic concentrations required to reduce biofilm load. A novel biofilm system – the alginate bead method will be used for these experiments, The alginate bead method was developed by a previous student in the Gallagher Laboratory, due to a need to have a reliable, robust and inexpensive technique to examine formation of biofilms and antibiotic resistance. There are devices and assays available, such as the Calgary Biofilm Device, which are extensively used for these purposes. However, the cost is prohibitive. This thesis found that the development of biofilms occurs much earlier than expected, with stable, fixed formation after just four hours of growth. Depending upon the antibiotic, resistance can develop within the first two hours of growth and thereafter steadily increases. By 24 hours the biofilms are fully resistant to all the tested antibiotics. In mixed species biofilms, the two species act synergistically protecting each other against the antibiotics, resulting in a much higher antibiotic concentration required. Common antibiotics used to treat staphylococcal infections are often combined to enhance their destructive effect and prevent the development of resistance. The effects of these antibiotics, when combined was explored. Biofilm resistance against gentamicin, one of the most common antibiotics used to treat staphylococcal infections develops quickly. However, when combined with other antibiotics gentamicin resistance is delayed. As antibiotic concentrations have to be extremely high in order to have any effect on established biofilms, alternative methods need to be investigated. Any alternative approaches would be employed in conjunction with conventional therapies preventing stable biofilm formation and disrupting established biofilms. Such methods may include sugar metabolites, enzymatic disruption, D-amino acids and activation of the quorum sensing system. The main conclusion which can be taken from this work are that firstly the alginate bead method of a viable, suitable alternative to the Calgary Biofilm Device and supports biofilm formation and testing. Secondly that biofilms form and are resistant to antibiotics much earlier than expected, and extreme concentrations of antibiotics are required to have an effect. Thus the inclusion of alternative methods which disrupt biofilms would be beneficial to clinical practice. However, the alternative methods investigated within this thesis (D-amino acids and sugar metabolites) failed to show any inhibition of biofilms. There are other possible choices which would need to be investigated.

Micropartícula de quitosana complexada com íons metálicos [Fe(II), Fe(III), Zn(II)] foram preparadas e caracterizadas a fim de se obter sistemas microparticulados para a adsorção de substâncias. A técnica de preparo utilizada foi a secagem por aspersão, através da qual se obteve micropartículas esféricas colapsadas e com superfície rugosa. O tamanho de partícula foi influenciado tanto pela reação de reticulação com glutaraldeído como pela presença e tipo do metal utilizado para a formação do complexo. A adsorção do ciprofloxacino pelas micropartículas desenvolvidas foi estudada em meio aquoso, O estado de equilíbrio foi influenciado pelo tipo de metal presente na micropartícula e pela concentração inicial de ciprofloxacino na solução. Com o intuito de descrever o mecanismo de adsorção, foram utilizados modelos matemáticos de isotermas de Langmuir e Freundlich, sendo que os dados apresentaram um melhor ajuste para a isoterma de Freundlich. Através da análise de modelos de cinética de pesudo-primeira-ordem e pseudo-segunda-ordem, verificou-se que os dados melhor se ajustaram ao modelo de pseudo-segunda-ordem, indicando que o mecanismo de adsorção do ciprofloxacino pelas micropartículas é através de quimissorção. A determinação da capacidade de adsorção do ciprofloxacino, conduzido in vitro, demonstrou que as micropartículas de quitosana-Fe(III) e quitosana-Zn(II) apresentam efetividade de adsorção. Com isso as micropartículas de quitosana-Fe(III) foram encapsuladas por uma matriz de pectina, sendo este utilizado para a adsorção de antimicrobianos residuais presentes no cólon. A estabilidade das esferas foi determinada em meios digestivos simulados, onde se verificou uma estabilidade de 1 h e 5 h nos meios gástricos e intestinal, respectivamente. Quando as esferas foram incubadas no meio colônico, observou-se uma degradação dependente da concentração de pectina. Com o intuito de evitar a adsorção do ciprofloxacino no meio intestinal, as esferas foram revestidas com Eudragit RS. Estudos de adsorção em meio colônico simulado demonstrou que a capacidade de adsorção das micropartículas de quitosana-Fe(III) não é afeta pela encapsulação na matriz de pectina. O sistema desenvolvido demonstra ser promissor para a extração do ciprofloxacino presente no meio colônico simulado. / The aim of this work was to develop, characterize chitosan- metal ion [Fe(II), Fe(III), Zn(II)] microparticle, and evaluate the adsorption capacities of ciprofloxacin by these complexes. The microparticles were prepared by a spray drying method. They showed good sphericity and a roughness surface morphology. The particle size was influenced by crosslinking reaction and by the kind of metal ion onto the microparticle. A batch adsorption system was applied to study the adsorption of ciprofloxacin from aqueous solution by chitosan-metal ion crosslinked microparticle. The adsorption process was fast, and the equilibrium contact times were influenced by the kind of metal ion onto microparticle. The Langmuir and Freundlich adsorption models were used for mathematical description of the adsorption equilibrium, and it was found that experimental data fitted well to Freundlich model. Adsorption models, based on the assumption of the pseudo-first-order and pseudo-second-order mechanism showed that the pseudo-second-order adsorption mechanism is predominant, and the adsorption process appears to be controlled by the chemical reaction. Chitosan-Fe(III) and chitosan-Zn(II) microparticle demonstrated the highest adsorption of ciprofloxacin. Chitosan-Fe(III) microparticle was encapsulated in a pectin matrix. The system was used for the adsorption of colonic residual antibiotics responsible by the emergence of resistance. The stability of the beads was carried out on simulated digestive media. Beads incubated in simulated gastric and intestinal medium were stable for 1 h and 5 h, respectively. When incubated in simulated colonic medium, beads were then degraded by pectinases contained in the medium. Coating with Eudragit RS was needed to prevent the early adsorption of antibiotics in intestinal medium. Adsorption studies in simulated colonic medium show that the adsorption capacity of chitosan-Fe(III) is not modified after encapsulation within pectin beads making the elimination reaching the colon clinically feasible.