Gelation properties of a salt extracted pea (Pisum sativum) protein isolate (PPIs) were evaluated with a goal of using this isolate as a meat extender. Microbial transglutaminase (MTG) was used to improve gelation of PPIs, muscle protein isolate (MPI) from chicken breast and the two combined. Gelation properties were evaluated using small amplitude oscillatory rheology and texture analysis. SDS-PAGE and differential scanning calorimetry were used to examine protein structure. Minimum gelation concentration for PPIs was 5%, lower than the 14% obtained for a commercial pea protein isolate (PPIc), possibly because the PPIc undergone denaturation whereas PPIs had not. Storage modulus (G') and loss modulus (G") increased with protein concentration and maximum gel strength for PPIs occurred at pH 4.0 in 0.3M NaCl. Higher or lower pH values affected protein charge and the potential for network formation. Higher salt concentrations resulted in increased denaturation temperatures, to a point where the proteins did not denature at the 95ºC temperature used for gel formation. When both heating and cooling rate were increased, gel strength decreased, though the cooling rate had a greater impact. Chaotropic salts enhanced gel strength, whereas non-chaotropic salts stabilized protein structure and decreased gel formation. Based on effects of guanidine hydrochloride, urea, propylene glycol, β-mercaptoethanol, dithiothreitol and N-ethylmaleimide, hydrophobic and electrostatic interaction and hydrogen bonds were involved in pea protein gel formation but disulfide bond contribution was minimal. Gels formed with MPI at concentrations as low as 0.5% and were strongest at 95ºC, higher than the ~ 65ºC normally used in meat processing. Good gels were formed at pH 6 with 0.6 to 1.2 M NaCl. Addition of MTG increased gel strength for PPIs, MPI, and a combination of the two. SDS-PAGE showed that bands in the 35~100kDa range became fainter with higher MTG levels but no new bands were found to provide direct evidence of interaction between muscle and pea proteins. Improved gel strength for the MPI/PPI mixture (3:1) containing MTG suggested that some crosslinking occurred. Higher heating temperatures and MTG addition led to the formation of MPI/PPI gel and demonstrated the potential for utilization of pea protein in muscle foods.

The arrangement of soft materials through solution processing techniques is a topic of profound importance for next generation solar cells; the resulting morphology has a major influence on construction, performance and lifetime. This thesis investigates the connections between the soft matter physics of colloidal systems and solid state dye sensitised (SSDS) and bulk heterojunction (BHJ) solar cells. A study of aqueous titanium dioxide nanoparticulate suspensions was carried out in order to observe how suspension structure can be controlled by altering the inter-colloid potential via pH-induced electrostatic charging. Measurements were performed at volume fractions between 0.025% and 8.2% with the solution pH set to 3.1, 3.5 or 4.5 before mixing. Suspensions with a volume fraction above 4% formed self-supporting gels regardless of the set pre-mix pH. These gels displayed shear thinning behaviour with a power law exponent of 0.8, a yield stress of 11(1) Pa and rheological response consistent with an aggregated fractal network. At lower volume fractions, suspensions exhibited consolidation interpreted as the collapse of a gel of fractal clusters with a fractal dimension of 2.36. The velocity of the suspension/supernatant interface exhibited delayed sedimentation behaviour, as well as further fractal-based power law scalings with volume fraction. Lower volume fraction suspensions were explored using dynamic light scattering. Limited aggregation of ‘stable’ suspensions was observed when compared to primary aggregate radii measured from electron microscopy images. To connect suspension structure and cell manufacture, the behaviour of more concentrated suspensions was observed during the drying of thin films, a process which forms an essential part of a SSDS solar cell. Lowering the pH of the suspension after mixing from 4 to 3 resulted in an ordering of observed crack domains. An increase in film delamination was also observed. Rates of mass loss during drying followed the expected three phase process, although there was an unexpected increase in rate during the initial phase (where rate is usually constant in time). Dynamic light scattering was found to be a useful but demanding technique for studying cluster formation in titanium dioxide suspensions. A non-linear fitting technique utilising the method of moments was thoroughly explored using computer simulated datasets. The algorithm reduced the systematic error in fitted parameters for moderately polydisperse (0:2 < < 0:4) datasets as compared to the commonly applied linear algorithm. The fitting algorithm was also robust to bad initial estimates of parameters. Finally, test solar cells have been built using blends of titanium dioxide and poly-3-hexylthiophene. Device performance was reduced with blend standing time after mixing but could be improved by remixing the blend before spin coating, implicating a reversible process (e.g. aggregation of titanium dioxide or crystallisation of P3HT) in the loss of performance. Addition of a titanium dioxide hole blocking layer before spin coating reduced cell performance. Combining the above studies and these device designs provides a future platform for continuation of this work in the context of real devices.

Chitosan has proven through the years as a versatile biomaterial to be used in pharmaceutical applications. Its mucoadhesive properties as well as its ability to manipulate the tight junctions in epithelium membranes have qualified it as an effective drug carrier in controlled drug delivery systems. Microparticles or beads as they are forward called in this study have advantages over conventional drug dosage forms because of a large surface to volume ratio and have the ability to target a specific site for drug release. Indomethacin is an anti-inflammatory drug that causes gastrointestinal side effects in conventional immediate-release dosage forms. The goal is to manipulate the drug delivery vehicle to target the intestines/colon as the site for drug delivery and to minimize this side effect. Thus chitosan beads have been chosen as a drug delivery system for indomethacin in this study. Chitosan beads have been prepared through the ionotropic gelation method using tripolyphophate (TPP) as a cross-linking agent. To prepare the most effective bead to encapsulate indomethacin different formulation and system variables (pH of the TPP solution, the concentration of the TPP solution as well as the indomethacin concentration) have been evaluated according to the following parameters: morphology, drug loading capacity and swelling capability. The ideal pH of the TPP solution was determined at 8.7 and the most effective TPP and indomethacin concentration were 5% w/v and 4% w/v respectively. The chitosan concentration was kept at 3% w/v throughout the study. These concentrations were used to examine the effect of pharmaceutical excipients on the indomethacin release from chitosan beads. The effect of the different excipients namely, ExplotabⒽ(0.25% w/v), Ac-Di-SolⓀ (0.5% w/v) and Vitamin C (0.25% w/v), on the morphology, drug loading capacity, swelling capability as well as the drug release of indomethacin chitosan beads (ICB's) were also studied. The excipients were used in the individually above mentioned concentrations and in combination with each other in the same concentrations. These formulations were used in dissolution studies over a period of 6 hours in PBS pH 7.4 solutions. The indomethacin release rate increased when an excipient was added to the formulation and it dramatically increased when the excipients were added in their various combinations, compared to the formulation that did not contain excipients. / Contents: Chitosan -- Controlled drug delivery -- Indomethacin -- Inotropic gelation -- Tripolyphosphate (TPP) -- Explotab® -- Ac-Di-Sol® -- Vitamin C / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

Controlled release systems aim at achieving a predictable and reproducible drug release over a desired time period. These systems allow reduced dosing frequency, constant drug levels in the blood, increased patient compliance and decreased adverse effects. In a recent study, Chitosan beads, containing N-trimethyl Chitosan chloride, have shown a potential in the delivery of rifampicin. However, because of inadequate amounts of rifampicin released over 24 hours, incorporation of other pharmaceutical excipients to increase the swelling behaviour of the beads to improve drug release, was considered in this study. Chitosan beads were prepared through ionotropic gelation with tripolyphosphate (TPP) as a crosslinking agent. To increase the porosity if the Chitosan beads Explotab®, Ac-Di-Sol® and vitamin C were added individually to Chitosan solutions at concentrations of 0.1, 0.25 and 0.5 % w/v before adding the mixture to the TPP solution. Swelling and morphology studies were used in the evaluation of the different formulations. The swelling and morphology results were then used to select a set of combination and concentrations of two excipients sand then prepare and characterise beads containing two combinations. The combination formulations and formulations containing single excipients were then loaded with rifampicin. Pure chitosan beads exhibited a higher drug loading capacity (67.49 %) compared to the lowest loading capacity of 41.61 % exhibited by chitosan beads containing a combination of Explotab®, Ac-Di-Sol®.For all the other formulations the drug loading capacity ranged within 48 and 63 %. These formulations were used for dissolution studies over a period of 6 hours at pH 5.60 and 7.40. The dissolution results showed that no chitosan has dissolved at both pH values. A significant amount of rifampicin was, however, released from the beads, especially at pH 7.40. chitosan beads containing vitamin C also exhibited high rifampicin release (48.34 ± 1.00) %) at pH 5.60 compared to the other formulations and this makes vitamin C a potential excipient for enhanced drug release over a wide pH range (both acidic and alkalinic). However, further studies are necessary to optimise the preparation method to minimise drug loss during loading and to improve the drug loading capacity of the beads. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2005.

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.

In controlled release applications a drug is molecularly dispersed in a polymer phase. In the presence of a thermodynamically compatible solvent, swelling occurs and the polymer releases its content to the surrounding medium. The rate of the drug release can be controlled by interfering with the swelling rate of the beads or by influencing diffusion through the viscosity of the polymer. Beads that contain chitosan were prepared through the ionotropic gelation method where tripolyphosphate (TPP) was used as the crosslinking agent. Beads that consisted of 3% w/v isoniazid (lNH) and 5% w/v chitosan were prepared in a 5% w/v TPP solution (pH 8.7) as the primary beads. To improve the drug loading of chitosan isoniazid beads (ClB) the TPP concentration, pH of the TPP solution and the INH concentrations were altered for maximum drug loading. To increase the porosity of the beads of chitosan beads Explotab® (EXPL), Ac-Di-Sol® (ADS) and Vitamin C (VC) were added individually to chitosan solutions at concentrations of 0.1, 0.25 and 0.5% w/v before adding the mixture to the TPP solution. Morphology, swelling and drug loading studies were used to evaluate the different formulations. After these excipients were added individually they were also added in combinations of two excipients respectively and characterised. From the results of the drug loading studies the beads that contained only chitosan and isoniazid showed a percentage drug loading of (43.92%) which is the best of all the beads that were analyzed. The multi excipient combination of Ac-Di-Sol® and Explotab® showed the best swelling capability at both pH levels. Dissolution studies were conducted on all the formu lations over a period of 6 hours (360 minutes) at pH 5.6 and pH 7.4. From the dissolution results it were clear that no chitosan dissolved at both pH values. The dissolution of single pharmaceutical excipient (SPE) and multi pharmaceutical excipient (MPE) formulations can be arranged in the following order: VC/ADS < VC < ADS/EXPL < ADS < VC/EXPL < CIB < EXPL. Explotab® is a potential excipient for enhanced drug release over a wide pH range. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

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.

Gelation properties of a salt extracted pea (Pisum sativum) protein isolate (PPIs) were evaluated with a goal of using this isolate as a meat extender. Microbial transglutaminase (MTG) was used to improve gelation of PPIs, muscle protein isolate (MPI) from chicken breast and the two combined. Gelation properties were evaluated using small amplitude oscillatory rheology and texture analysis. SDS-PAGE and differential scanning calorimetry were used to examine protein structure. Minimum gelation concentration for PPIs was 5%, lower than the 14% obtained for a commercial pea protein isolate (PPIc), possibly because the PPIc undergone denaturation whereas PPIs had not. Storage modulus (G') and loss modulus (G") increased with protein concentration and maximum gel strength for PPIs occurred at pH 4.0 in 0.3M NaCl. Higher or lower pH values affected protein charge and the potential for network formation. Higher salt concentrations resulted in increased denaturation temperatures, to a point where the proteins did not denature at the 95ºC temperature used for gel formation. When both heating and cooling rate were increased, gel strength decreased, though the cooling rate had a greater impact. Chaotropic salts enhanced gel strength, whereas non-chaotropic salts stabilized protein structure and decreased gel formation. Based on effects of guanidine hydrochloride, urea, propylene glycol, β-mercaptoethanol, dithiothreitol and N-ethylmaleimide, hydrophobic and electrostatic interaction and hydrogen bonds were involved in pea protein gel formation but disulfide bond contribution was minimal. Gels formed with MPI at concentrations as low as 0.5% and were strongest at 95ºC, higher than the ~ 65ºC normally used in meat processing. Good gels were formed at pH 6 with 0.6 to 1.2 M NaCl. Addition of MTG increased gel strength for PPIs, MPI, and a combination of the two. SDS-PAGE showed that bands in the 35~100kDa range became fainter with higher MTG levels but no new bands were found to provide direct evidence of interaction between muscle and pea proteins. Improved gel strength for the MPI/PPI mixture (3:1) containing MTG suggested that some crosslinking occurred. Higher heating temperatures and MTG addition led to the formation of MPI/PPI gel and demonstrated the potential for utilization of pea protein in muscle foods.

The rheological, color, micro-structural, and electrical properties of surimi seafood gels were investigated. Various starches and protein additives at different ratios were evaluated with Alaska pollock surimi under ohmic heating at different heating rates to determine their functional properties and further to compare these properties with those of conventionally cooked gels. Native starches at low concentration were able to enhance rheological properties due to their gelatinization during heating. Pregelatinized starch decreased texture properties; however, it could suppress the undesirable appearance of the final product because its granules could absorb the surrounding water during chopping and perform a higher degree of retrogradation when cooling. A mixture of native and pregelatinized starches showed a positive trend at high concentration. The more starch added, the lower the L* and b* values of the gels. Protein additives improved textural properties, but negatively affected gel colors. Lower moisture content of the final products showed higher strength in texture, but lower lightness values. Gels cooked under ohmic heating with a slow heating rate mostly exhibited better texture properties than conventionally cooked gels. Electrical conductivities increased when temperature increased, resulting in a linear relationship. Electrical conductivity also significantly increased with moisture content, and slightly increased with applied frequency and voltage. There were some changes in the magnitude of electrical conductivity of surimi-starch paste when temperature increased, most obviously seen at a high concentration of native starch with slow ohmic heating. This indicated that starch gelatinization affected the electrical conductivity of surimi-starch paste while heating. / Graduation date: 2003

L'implantation d'îlots de Langerhans microencapsulés est une thérapie prometteuse pour le diabète de type 1. Le concept est de rétablir la fonction de sécrétion d'insuline tout en évitant le rejet de greffe. Les premiers essais cliniques ont reporté des résultats encourageants mais encore peu reproductibles. En effet, les techniques actuelles de production de microcapsules sont manuelles et au sein d'un même lot les capsules ne sont pas homogènes. L'utilisation de la microfluidique offre la possibilité de remédier à ce problème. Ce projet présente les différentes étapes d'optimisation d'un système microfluidique complexe qui automatise le procédé d'encapsulation monocouche de cellules dans des capsules polymériques d'alginate. Ce système comporte trois fonctions principales en série : la formation de gouttes monodisperses d'alginate en flux d'huile par un module MFFD (Micro Flow Focusing Device), le transfert de ces gouttes de la phase huileuse vers une phase aqueuse gélifiante de calcium et enfin un second transfert vers un flux à concentration physiologique. Des capsules monodisperses et sphériques ont été obtenues en sortie de ce système et des premiers tests d'encapsulation de cellules ont été réalisés. Les capsules produites par le système automatisé ont conduit à une première implantation chez le rongeur. Ce système est une première étape clé vers un dispositif instrumenté qui permettrait aux cliniciens d'encapsuler des îlots rapidement et de façon reproductible directement après leur isolement, puis de les implanter chez les patients diabétiques. Mots clés : encapsulation, îlots de Langerhans, alginate, gélification, microfluidique, automatisation, MFFD, transfert de phase. / Epileptic seizures arise from pathological synchronization of neuronal ensemble.Seizures originating from primary motor cortex are often pharmacoresistant, and many times unsuitable for respective surgery because of location of epileptic focus in eloquent area. Basal ganglia play important role in seizure propagation. Micro electrode recordings performed during previous studies indicated that input structures of basal ganglia such as GPe, Putamen and Subthalamic nucleus (STN) are strongly modified during seizures. For example the mean firing rate of neurons of the STN and Putamen increased and the percentage of oscillatory neurons synchronized with the ictal EEG was higher during seizures as compared to interictal periods. Pilot studies in humans have shown the possible beneficial effect of chronic DBS applied to STN in treatment of pharmacoresistant motor seizures. Our study was aimed at studying the therapeutic effect of electrical stimulation of input structures of basal ganglia . We first developed a stable, predictable primate model of focal motor epilepsy by intracortical injection of penicillin and we documented it's pharmacoresistence. We then stereotactically implanted DBS electrodes in the STN and Putamen. The stimulator was embedded at the back of the animals. Subthreshold electrical stimulations at 130 Hz were applied to STN. Stimulator was turned ON when penicillin was injected. Sham stimulation at 0 volt was used as a control situation, each monkey being its own control. The time course, number and duration of seizures occurring in each epochs of 1 h were compared during ON and sham stimulation periods. Each experimental session lasted uptoo 6 hours,We also studied preventive high frequency stimulation of STN and subthershold low frequency stimulation of Putamen with 5 Hz and 20 Hz in the same model .Finally we studied combined effects of high frequency STN and low frequency Putamen stimulation in one monkey Results: Data was analysed from 1572 seizures in 30 experiments in three monkeys for chronic STN stimulation , 454 seizures in 10 experiments in one moneky during preventive STN stimulation ,289 seizures from 14 experiments in two monkeys during LFS putamen stimulation and 477 seizures from 10 sessions during combined STN and Putamen stimulation in one monkey The best results were observed during chronic STN stimulation The occurrence of first seizure was significantly delayed as compared to sham situation. Total time spent in focal seizures was significantly reduced by ≥69% on an average (p ≤0.05) after STN stimulation, due to a significant decrease in the number of seizures especially so during the first 3 hours after stimulation. The duration of individual seizures reduced moderately. Bipolar and monopolar stimulation modes were equally effective Preventive HFS STN (in one specimen) was not found to be superior to acute stimulation. LFS Putamen alone was effective but mainly in first two hours of stimulation .In a combined HFS STN and LFS Putamen stimulation the effect of stimulation in terms of seizure control was modest and poor compared to HFS STN alone or LFS Putamen alone. This study provides original data in primates showing the potential therapeutic effect of chronic HFS-STN DBS to treat focal motor seizures . A discussion explaining these