In this work, we have analysed the temporal dynamics of gut-dwelling bacteria and Borrelia in the gut of the deer tick Ixodes ricinus. Using quantitative PCR, we have shown that levels of the tick intestinal microflora are profoundly decreased at later stages of feeding on whole blood but not on serum. Even though we noted that host complement system manages to interfere with Borrelia viability in vitro, we did not see any effect of host complement on Borrelia acquisition in adult ticks in vivo. However, we revealed that host hemoglobin is essential for Borrelia proliferation in the tick gut. All together, these data imply that, during feeding, levels of gut-dwelling bacteria and Borrelia are determined by the host. While hemoglobin seems to be detrimental for gut-dwelling bacteria, Borrelia require it in order to proliferate. During off-host stage, we showed that levels of gut-dwelling microflora are regulated by an intestinal transmembrane enzyme Dual oxidase. In conclusion, we aimed, and mostly succeeded, to perform pilot experiments describing the biology of a complex process of regulating gut microflora in the vector Ixodes ricinus and extend it by its impact on Borrelia acquisition

Einleitung Streptococcus (S.) suis ist weltweit in Schweinepopulationen verbreitet. S. suis verursacht hohe wirtschaftliche Verluste durch das Auftreten von Meningitis, Arthritis, Serositis und Endokarditis und stellt als Zoonoseerreger gleichzeitig ein Risiko für den Menschen dar. Im Zusammenhang mit Infektionen in europäischen Schweinebetrieben werden Serotyp 2, 7 und 9 am häufigsten nachgewiesen. Die Bakteriämie spielt eine Schlüsselrolle in der invasiven S. suis Erkrankung und die Interaktion der Streptokokken mit den Immunzellen des Wirts im Blut ist entscheidend für den Ausgang der Infektion. Ziele der Untersuchung Das Ziel der vorliegenden Arbeit, war die Untersuchung der Fähigkeit von porzinen Immunzellen S. suis durch Phagozytose und reaktive Sauerstoffspezies (ROS) zu töten. Dabei wurden vor allem die Bedeutung von IgM und des Komplementsystems beleuchtet. In diesem Sinne, wurde auch die Arbeitshypothese untersucht, dass eine Modifizierung der bakteriellen Zellwand durch D-Alanylierung von Lipoteichonsäuren (LTAs) S. suis hilft, angeborene Immunfunktionen zu umgehen, wie z. B. die Opsonisierung mit Komplementfaktoren, sowie dass diese Zellwandveränderung die Interaktion von S. suis mit Leukozyten beeinflusst. Material und Methoden Die Bestimmung von ROS und dem Überleben der Streptokokken wurde in vivo im Blut zweier mit S. suis-infizierter Ferkel und in vitro in einem rekonstituierten Blutmodel durchgeführt. Die ROS-Messung erfolgte unter Zugabe von Dihydrorhodamine 123 mittels Durchflusszytometrie in Granulozyten. Verschiedene Inhibitoren wurden dabei eingesetzt: Apocynin um die NADPH Oxidase und damit die ROS-Bildung zu hemmen, Vaccinia Virus Complement Control Protein (VCP) für die Inaktivierung der Komplementkaskade und IdeSsuis um porzines IgM zu spalten. Mithilfe eines thermosensitiven Vektors wurde eine isogene Deletionsmutante des dltA Gens erstellt, um den Einfluss der D-Alanylierung von LTAs zu untersuchen. Die Sequenzierung des entsprechenden Genabschnitts und ein Southern Blot dienten der genetischen Verifizierung der Mutante. Weiterhin wurden Wachstumsverhalten, Hydrophobie und Ladung der Oberfläche sowie minimale Hemmkonzentrationen einer Reihe antimikrobieller Peptide für die dltA Mutante untersucht. Die Assoziation von Blutleukozyten mit S. suis wurde mithilfe von Far Red markierten Bakterien in der Durchflusszytometrie bestimmt. Die Zytokin-Messung erfolgte mit kommerziell erhältlichen Enzyme-linked immunosorbent assays (ELISA)-Kits. Ergebnisse S. suis Stämme der Serotypen 2, 7 und 9 zeigten sich hochsensibel gegenüber Wasserstoffperoxid. Eine Hemmung der Bildung von ROS in rekonstituierten Blutproben führte selbst in Anwesenheit einer hohen Konzentration von S. suis-spezifischen Antikörpern zu einem signifikanten Anstieg des bakteriellen Überlebens. Die Induktion von ROS durch S. suis in Granulozyten wurde durch spezifische Antikörper verstärkt und hing partiell von der Anwesenheit funktionellen Komplements ab. In der Abwesenheit von IgG reduzierte die Spaltung von IgM oder die Inaktivierung von Komplement die ROS Produktion um mehr als das Dreifache, was in einem Anstieg des bakteriellen Überlebens resultierte. Der Mechanismus von S. suis D-Alanin in seine LTAs einzulagern, erhöhte die Hydrophobie der bakteriellen Oberfläche und reduzierte die Opsonisierung mit Komplementfaktor C3b, sowie die Phagozytose durch Granulozyten in Vollblut und die Assoziation von S. suis mit Monozyten and Lymphozyten. Trotzdem wurde das Überleben der Streptokokken in Blut, welches S. suis-spezifische Antikörper enthielt, nicht signifikant durch diese Zellwandmodifikation gesteigert. Allerdings war der durch die dltA Mutante induzierte Gehalt an IL-1β im Blut signifikant geringer als der durch den Wildtyp induzierte. Hohe Antikörperspiegel verursachten einen hochsignifikanten Anstieg der Interaktion von S. suis mit Monozyten, was bei diesen zum inflammatorischen Zelltod mit einer starken Sekretion von IL-1β und TNF-α führte. Schlussfolgerung Trotz einer Vielzahl an Abwehrmechanismen von S. suis gegen oxidativen Stress, stellen Phagozytose und ROS einen sehr effektiven Mechanismus des Immunsystems dar, um die eingedrungenen Streptokokken zu töten. Die Induktion von ROS durch S. suis hängt dabei stark von der Anwesenheit spezifischer Antikörper und teilweise von aktivem Komplement ab. Die Fähigkeit von S. suis D-Alanin in seine LTAs einzulagern, verändert Eigenschaften der bakteriellen Zellwand und vermittelt dabei Schutz vor angeborenen Immunmechanismen, wie antimikrobiellen Peptiden und dem Komplementsystem, aber sie sorgt nicht für ein besseres Überleben der Streptokokken, in der Anwesenheit von spezifischen Immunglobulinen. Sie reduziert die Assoziation von S. suis mit Monozyten, was etwas in Diskrepanz zu einer 2000 postulierten modifizierten „Trojanisches Pferd“-Theorie steht. Die durch LTA D-Alanylierung gesteigerte IL 1β Sekretion im Vollblut, führt zu der Schlussfolgerung, dass S. suis durch diese Zellwandmodifikation Entzündungsprozesse im Wirt beeinflusst.:Contents 1 Introduction 2 Literature 2.1 Streptococcus suis 2.1.1 Characteristics and classification 2.1.2 Epidemiology and Pathology 2.1.3 Pathogenesis of S. suis infection 2.1.4 Cell wall modifications of S. suis 2.2 Selected aspects of the porcine blood immune system 2.2.1 Characteristics and components of porcine blood 2.2.2 Innate immunity 2.2.2.1 Cellular innate immunity in blood 2.2.2.2 Humoral innate immunity in blood 2.2.3 Adaptive immunity 2.2.3.1 Cellular adaptive immunity in blood 2.2.3.2 Humoral adaptive immunity in blood 2.3 Interaction of S. suis with the blood immune system 2.3.1 Immune evasion strategies against blood leukocytes 2.3.2 Complement evasion and S. suis cell wall modifications 3 Publications 3.1 Survival of Streptococcus suis in Porcine Blood Is Limited by the Antibody- and Complement-Dependent Oxidative Burst Response of Granulocytes 3.2 D-Alanylation of Lipoteichoic Acids in Streptococcus suis Reduces Association with Leukocytes in Porcine Blood 4 Discussion 4.1 Phagocytosis and oxidative burst in porcine blood 4.2 Interaction of S. suis with blood monocytes and lymphocytes 4.3 Conclusion 5 Zusammenfassung 6 Summary 7 References 8 Appendix 8.1 Presentations given during the development of this thesis / Introduction Streptococcus (S.) suis is a widespread pathobiont in the porcine population. It is reason for high economic losses in the swine industry by causing meningitis, arthritis, serositis, and endocarditis, but also poses a threat to human health as a zoonotic pathogen. Serotype 2, 7 and 9 play an important role in European disease cases on pig farms. Bacteremia is a hallmark of invasive S. suis infections and the interaction of the streptococci with blood immune cells is crucial for the outcome of infection. Aim of the study The objective of this thesis was to investigate the ability of porcine blood immune cells to kill S. suis by phagocytosis and oxidative burst and the importance of IgM and the complement system in the killing process. In this context, I investigated the working hypothesis that modifying its cell wall by D-alanylation of lipoteichoic acids (LTAs) aids S. suis to evade certain functions of innate immunity, like opsonization with complement components, and influences the interaction of S. suis with blood leukocytes. Materials and Methods The investigation of reactive oxygen species (ROS) and colony forming units (CFU) was performed in vivo in the blood of two S. suis-infected piglets and in vitro in a reconstituted blood model. ROS were measured by addition of dihydrorhodamine 123 and flow cytometry analysis of granulocytes. To analyze the influence of immunological components, different inhibitors were used: apocynin inhibits the NADPH oxidase and therefore the ROS production, vaccinia virus complement control protein (VCP) inhibits the complement cascade and IdeSsuis cleaves porcine IgM. To investigate the role of D-alanylation of S. suis-LTA an isogenic in-frame deletion mutant of the dltA gene, ΔdltA, was generated by using a thermosensitive shuttle vector. It was genetically verified by sequencing of the respective gene sequence and southern blotting. Phenotypical characterization included growth behavior, evaluation of surface hydrophobicity and electric charge and minimal inhibitory concentrations of a number of antimicrobial peptides. The association of blood leukocytes with S. suis was investigated by flow cytometry, using Far Red-labeled S. suis stocks. Cytokines were detected by commercially available Enzyme-linked immunosorbent assays (ELISA). Results S. suis strains of serotype 2, 7 and 9 were shown to be highly susceptible to oxidative burst intermediate hydrogen peroxide and inhibition of oxidative burst in reconstituted blood samples led to a significant increase of bacterial survival, even in the presence of high S. suis-specific antibody levels. The induction of ROS in granulocytes in response to S. suis was enhanced by specific antibodies and partially depended on the presence of functional complement. In the absence of IgG, IgM cleavage or complement inactivation both reduced the ROS production more than 3-fold and resulted in increased bacterial survival in accordance with an IgM-complement-oxidative burst axis. The mechanism of S. suis to introduce D-alanine into its LTAs increased the hydrophobicity of its surface, reduced opsonization with complement factor C3b, reduced phagocytosis by granulocytes in whole blood and association with monocytes and lymphocytes in isolated peripheral blood mononuclear cells. Nevertheless, in whole blood containing S. suis-specific antibodies, survival of the streptococci was not significantly increased by this cell wall modification, but levels of IL-1β induced by ΔdltA were significantly lower than those induced by the wt. High antibody levels caused a highly significant increase in the interaction of S. suis with monocytes in isolated PBMCs leading to an inflammatory cell death associated with the secretion of high levels of IL-1β and TNF-α. Conclusion Despite numerous described defense mechanisms of S. suis against oxidative stress, phagocytosis and ROS represent a very effective way of the porcine immune system to kill the invading streptococci. The induction of ROS by S. suis is highly dependent on the presence of specific antibodies and partially depends on active complement. The ability of S. suis to D-alanylate its LTAs changes surface properties of S. suis and provides protection from innate host defenses like antimicrobial peptides and the complement system, but does not help the bacteria to survive in the presence of specific immunoglobulins. It reduces the association with monocytes, in contradiction to a proposed “modified trojan horse theory”. The increased IL-1β production in response to S. suis, due to LTA D-alanylation, leads to the suggestion that this surface modification influences inflammatory processes is the host.:Contents 1 Introduction 2 Literature 2.1 Streptococcus suis 2.1.1 Characteristics and classification 2.1.2 Epidemiology and Pathology 2.1.3 Pathogenesis of S. suis infection 2.1.4 Cell wall modifications of S. suis 2.2 Selected aspects of the porcine blood immune system 2.2.1 Characteristics and components of porcine blood 2.2.2 Innate immunity 2.2.2.1 Cellular innate immunity in blood 2.2.2.2 Humoral innate immunity in blood 2.2.3 Adaptive immunity 2.2.3.1 Cellular adaptive immunity in blood 2.2.3.2 Humoral adaptive immunity in blood 2.3 Interaction of S. suis with the blood immune system 2.3.1 Immune evasion strategies against blood leukocytes 2.3.2 Complement evasion and S. suis cell wall modifications 3 Publications 3.1 Survival of Streptococcus suis in Porcine Blood Is Limited by the Antibody- and Complement-Dependent Oxidative Burst Response of Granulocytes 3.2 D-Alanylation of Lipoteichoic Acids in Streptococcus suis Reduces Association with Leukocytes in Porcine Blood 4 Discussion 4.1 Phagocytosis and oxidative burst in porcine blood 4.2 Interaction of S. suis with blood monocytes and lymphocytes 4.3 Conclusion 5 Zusammenfassung 6 Summary 7 References 8 Appendix 8.1 Presentations given during the development of this thesis

Artificiell intelligens blir allt mer vanligt inom fler och fler områden. Ett område där tekniken är relativt ny är inom kreativa processer och kreativa områden. Detta arbete är en kvalitativ studie av explorativ karaktär, som undersöker hur AI kan användas inom dessa kreativa processer samt vilka möjligheter och utmaningar som uppkommer av det. Tre intervjuer har genomförts med personer som har god och aktuell kunskap inom ämnet. Det insamlade materialet har sedan analyserats med den kreativa processen som ramverk. Resultatet visar att AI i vissa steg av processen kan användas, dels för att underlätta men också för att effektivisera densamma. I andra steg har utvecklingen av AI inte kommit tillräckligt långt för att bidra med något värde eller erbjuda någonting som utvecklar eller gör processen lättare. Vidare har resultatet visat att inställningen till användandet kan bli en avgörande faktor för fortsatt utveckling och användning, men även att möjligheterna är fler än utmaningarna.

Gegenstand der vorliegenden Arbeit ist die numerische Simulation piezoelektrischen Materialverhaltens, sowie spezieller Probleme aus der Mechanik (inkompressibles Materialverhalten) unter Anwendung der Methode der finiten Elemente. Hierbei wird die Strategie der adaptiven Netzsteuerung angewendet, welche mit Hilfe einer lokalisierten a-posteriori Fehlerschätzung erlaubt, den lokalen Feinheitsgrad der Diskretisierung den Besonderheiten der Aufgabenstellung anzupassen. Beide betrachteten Problemklassen führen nach der Diskretisierung und FEM auf Gleichungssysteme in spezieller Blockstruktur, die insgesamt symmetrisch, aber nicht positiv definit ist. Als Löser kann nicht der gewöhnliche CG verwendet werden, stattdessen wird eine Variante des Bramble-Pasciak-CGs benutzt, welcher als Speziallöser die Matrizenstruktur ausnutzt. Für diesen Löser wird eine Strategie zur Parameterwahl vorgeschlagen sowie die Wirksamkeit einer Vorkonditionierung im piezoelektrischen Fall theoretisch nachgewiesen. Weiterhin wird die FEM einschließlich Adaptivität für Piezomaterialien auf rotationssymmetrische Probleme erweitert, so daß diese spezielle Problemklasse zweidimensional gerechnet werden kann. Numerische Vergleiche mit echter 3D-Rechnung illustrieren enorme Vorteile in Genauigkeit und Rechenaufwand. Im letzten Kapitel werden in piezoelektrische Materialien hineinwachsende Risse betrachtet und entsprechende Anpassungen vorgenommen. Mit Wahl geeigneter Datenstrukturen und einer passenden Vorkonditionierung ist es möglich, eine Simulationssoftware bereitzustellen welche als Grundlage zum Test von Bruchkriterien verwendet werden kann. Die beschriebenen numerischen Methoden wurden in ein bestehendes adaptives 2D-FEM-Programm implementiert, und an ausgewählten Beispielen ein Vergleich mit einer analytischen Lösung durchgeführt sowie die Effektivität der Rechnung getestet.

Bordetella pertussis is a Gram-negative strictly human pathogen and the major causative agent of whooping cough or pertussis. The incidence of this highly contagious respiratory disease in developed countries has increased in the last decades. One of the less characterized virulence factors of B. pertussis is the type three secretion system (TTSS) which is responsible for the secretion of the effector proteins into host eukaryotic cells. This diploma thesis sheds light onto factors influencing TTSS in vitro activity. Although TTSS of laboratory strain Tohama I was induced by biologically active compounds present in blood (e. g. complement proteins), TTSS of recent clinical isolate B1917 seems to be induced permanently. Furthermore, BB0302 encoding a GntR family transcription regulator in B. bronchiseptica RB50 (homologous to BP0209 of Tohama I) was studied, however, the deletion of this gene did not affect the TTSS functionality. Serum resistance is a factor that plays a key role in the pathogenesis of B pertussis. We show that Czech recent isolates (2008-2015) are significantly more resistant to serum killing in vitro than the original vaccine strains (1954-1965). This phenomenon seems to result from the adaptation of global B. pertussis population to its human host. In addition, this diploma...

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Denna studie syftar att undersöka huruvida animation som visuellt komplement på Spotify väcker större engagemang emotionellt än ett statiskt skivomslag. Animerade filmer har tagits fram till sex olika låtar på albumet 99.9% av artisten Kaytranada. Detta har gjorts genom en förstudie i form av en enkät, samt research om de befintliga filmer som finns tillgängliga på Spotify i dagsläget. Efter detta har designarbetet utförts genom brainstorming, explorativt skissande och storyboards. För att utvärdera skapades en värderingsmatris med syfte att välja ut de mest engagerande idéerna, för att sedan fortsätta med digitalt skissande och slutligen animering. Efter detta värderades animationerna gentemot det statiska skivomslaget genom en kvalitativ enkät, såväl som två olika fokusgrupper. Resultatet visade att även om animationerna ansågs något repetitiva så ansåg en majoritet att de var mer engagerande emotionellt än ett statiskt skivomslag.

SYFTE: Syftet är att belysa patienternas upplevelse av läkemedelsfri smärtlindring med stöd av grindteorin. DESIGN: Litteraturstudie BAKGRUND: Kunskap om hur patienterna upplever läkemedelsfri smärtbehandling baserad på grindteorin, kan göra det lättare för den enskilda sjuksköterskan att fatta beslut om användande av dessa metoder. URVAL: Vetenskapliga artiklar med empiriska studier på vuxna publicerade mellan åren 2000-2012. METOD: Databassökningar och manuella sökningar RESULTAT: 14 studier med sammanlagt 1771 deltagarevisar att smärtlindringsmetoderna med stöd av grindteorin hade avsedd effekt på smärta. De gav även patienterna lindring vad avser oro och rädsla. Några av studierna tar även upp att patienterna fick en känsla av att själv kunna påverka smärtan. Metoderna som användes var såväl hudstimulerande, som kognitiva. SLUTSATS: Smärtlindring baserad på grindteorin, såväl hudstimulering som kognitiva metoder, är något som sjuksköterskan bör ha kunskap om och använda för att lindra smärta och oro/rädsla. Metoderna är även ett sätt att låta patienten känna sig delaktig, då speciellt de kognitiva metoderna. / PURPOSE: The aim is to illuminate the patients experience of non-pharmacological pain relief with support of the gate-control theory. DESIGN: Literature review/over-view BACKGROUND: Knowledge of how the patients experience non-pharmacological pain treatment based on the gate-control theory can make it easier for the individual nurse to make decisions on the use of these methods. SAMPLE: Scientific studies with empirical studies on adults, published in articles between 2000-2012 METHOD: Database- and manual searches FINDINGS: 14 studies with in total 1771 participants show that the pain relief methods with support of the gate-control theory had the intended effect on pain. They also gave the patients relief with regard to anxiety. Some of the studies also mention that the patients got a feeling of being able to affect the pain themselves. The methods used were skin-stimulating as well as cognitive. CONCLUSIONS: Pain relief based on the gate-control theory, skin-stimulating as well as cognitive methods, is something that the nurse should have knowledge about and use to relieve pain and anxiety. The methods are also a way of letting the patient feel involved, especially the cognitive methods.

Research on nanoparticles for pharmaceutical applications has become increasingly popular in recent years. N-trimethyl chitosan chloride (TMC) is a cationic polymer that can enhance absorption across mucosal surfaces. It has been explored as a nanoparticulate drug delivery system for the delivery of vaccines, vitamins, insulin and cancer medication. It has special interest for intravenous use, as it is soluble over a wide range of pH values. However, polycationic nanoparticles run a great risk for intravenous toxicity, as the positive surface charge allows easy electrostatic interactions with negatively charged blood components, such as red blood cells and plasma proteins. Additionally, the small size of the nanoparticles permits the binding of more proteins per mass, than larger particles do. These interactions can lead to extensive hemolysis, cell aggregation, complement activation, inflammation and fast clearance of the particles from the circulation. A decrease in the surface charge density can ameliorate these toxic interactions. Such a decrease is achieved by adding poly(ethylene) glycol (PEG) to the particle’s formulation. PEG creates a steric shield around the particles, preventing a certain extent of interaction between the particles and the blood components. To be able to use TMC nanoparticles as a successful drug delivery system, the hemocompatibility must first be determined, which was the aim of this study. The influence of particle size, concentration and the addition of PEG were also examined. The extent of hemolysis and cell aggregation caused by the experimental groups (20% and 60% concentration small TMC nanoparticles, 20% larger TMC nanoparticles and 20% cross-linked PEGTMC nanoparticles) were determined by incubating the groups with whole blood and/or blood components. Complement activation was determined with a Complement C3 Human enzyme-linked immunosorbent assay (ELISA) and plasma protein interactions were quantified through rapid equilibrium dialysis and a colorimetric assay. It was determined that 60% concentration small TMC nanoparticles caused 49.08 ± 2.538% hemolysis at the end of a 12-hour incubation period, significantly more than any other experimental group. This group had also caused mild aggregation of the white blood cells and platelets. This was the greatest extent of cell aggregation seen in any of the groups. No significant complement activation was seen by any of the experimental groups. Because of the cationic nature of the particles, all groups had more than 50% of the initial particles in the sample bound to plasma proteins after a 4-hour incubation period. However, at 90.68 ± 0.828%, the 60% small TMC nanoparticles had had significantly more interaction with the plasma proteins than the other groups. Through the experimental measurements it was revealed that TMC nanoparticles had hemotoxic effects at high concentrations. The addition of PEG to the particle formulation stabilized the particles and decreased their zeta potential , but had no significant effect on improving hemocompatibility. It was concluded that although further tests are needed, TMC nanoparticles seem to have potential as a successful intravenous carrier for high molecular weight active pharmaceutical ingredients. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2014

Research on nanoparticles for pharmaceutical applications has become increasingly popular in recent years. N-trimethyl chitosan chloride (TMC) is a cationic polymer that can enhance absorption across mucosal surfaces. It has been explored as a nanoparticulate drug delivery system for the delivery of vaccines, vitamins, insulin and cancer medication. It has special interest for intravenous use, as it is soluble over a wide range of pH values. However, polycationic nanoparticles run a great risk for intravenous toxicity, as the positive surface charge allows easy electrostatic interactions with negatively charged blood components, such as red blood cells and plasma proteins. Additionally, the small size of the nanoparticles permits the binding of more proteins per mass, than larger particles do. These interactions can lead to extensive hemolysis, cell aggregation, complement activation, inflammation and fast clearance of the particles from the circulation. A decrease in the surface charge density can ameliorate these toxic interactions. Such a decrease is achieved by adding poly(ethylene) glycol (PEG) to the particle’s formulation. PEG creates a steric shield around the particles, preventing a certain extent of interaction between the particles and the blood components. To be able to use TMC nanoparticles as a successful drug delivery system, the hemocompatibility must first be determined, which was the aim of this study. The influence of particle size, concentration and the addition of PEG were also examined. The extent of hemolysis and cell aggregation caused by the experimental groups (20% and 60% concentration small TMC nanoparticles, 20% larger TMC nanoparticles and 20% cross-linked PEGTMC nanoparticles) were determined by incubating the groups with whole blood and/or blood components. Complement activation was determined with a Complement C3 Human enzyme-linked immunosorbent assay (ELISA) and plasma protein interactions were quantified through rapid equilibrium dialysis and a colorimetric assay. It was determined that 60% concentration small TMC nanoparticles caused 49.08 ± 2.538% hemolysis at the end of a 12-hour incubation period, significantly more than any other experimental group. This group had also caused mild aggregation of the white blood cells and platelets. This was the greatest extent of cell aggregation seen in any of the groups. No significant complement activation was seen by any of the experimental groups. Because of the cationic nature of the particles, all groups had more than 50% of the initial particles in the sample bound to plasma proteins after a 4-hour incubation period. However, at 90.68 ± 0.828%, the 60% small TMC nanoparticles had had significantly more interaction with the plasma proteins than the other groups. Through the experimental measurements it was revealed that TMC nanoparticles had hemotoxic effects at high concentrations. The addition of PEG to the particle formulation stabilized the particles and decreased their zeta potential , but had no significant effect on improving hemocompatibility. It was concluded that although further tests are needed, TMC nanoparticles seem to have potential as a successful intravenous carrier for high molecular weight active pharmaceutical ingredients. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2014