Mesoporous materials constitute a promising class of nanomaterials for a number of applications due to their tunable pore structure. The synthesis of most mesoporous materials involves a surfactant liquid crystal structure to form the pores. As well as the many advantages associated with this method of synthesis, there are disadvantages such as high production costs and a substantial environmental impact which limit the possibilities for large scale production. Therefore there is a need for other synthesis routes. The aim of the work described herein was to contribute to this field by developing a synthesis route that does not rely on surfactants for pore formation. A mesoporous magnesium carbonate material was therefore formed by self-assemblage of the particles around carbon dioxide gas bubbles, which functioned as pore templates. It was also possible to vary the pore diameter between 3 and 20 nm. The biocompatibility of the formed magnesium carbonate material was evaluated in terms of in vitro cytotoxicity and hemocompatibility, in vivo skin irritation and acute systemic toxicity. The results from the in vitro cytotoxicity, in vivo skin irritation and acute systemic toxicity test using a polar extraction vehicle showed that the material was non-toxic. While signs of toxicity were observed in the acute systemic toxicity test using a non-polar solvent, this was attributed to injection of particles rather than toxic leachables. In the in vitro hemocompatibility test, no hemolytic activity was found with material concentrations of up to 1 mg/ml. It was further shown that the material had anticoagulant properties and induced moderate activation of the complement system. The anticoagulant properties were ascribed to uptake of Ca2+. Finally, the ability of the material to increase the dissolution rate of the poorly soluble drug itraconazole was analyzed.  Itraconazole was dissolved up to 23 times faster from the magnesium carbonate pores than when the free drug was used. The release rate from the delivery vehicle was dependent on the pore diameter. The work presented herein is expected to be useful for the development of alternative synthesis routes for mesoporous materials and also for encouraging the development of biomedical applications for these materials.

The surface of biomaterials can induce contacting blood to coagulate, similar to the response initiated by injured blood vessels to control blood loss. This poses a challenge to the use of biomaterials as the resulting coagulation can impair the performance of hemocompatible devices such as catheters, vascular stents and various extracorporeal tubings [1], what can moreover cause severe host reactions like embolism and infarction. Biomaterial induced coagulation processes limit the therapeutic use of medical products, what motivates the need for a better understanding of the basic mechanisms leading to this bio-incompatibility [2] in order to define modification strategies towards improved biomaterials [3]. Several approaches for the enhancement of hemocompatible surfaces include passive and active strategies for surface modifications. The materials’ chemical-physical properties like surface chemistry, wettability and polarity are parameters of passive modification approaches for improved hemocompatibility and are the focus of the present work. In the present study self assembled monolayers with different surface functionalities (-COOH, -OH, -CH3) were applied as well as two-component-layers with varying fractions of these, as they allow a defined graduation of surface wettability and charge. The ease of control over these parameters given by these model surfaces enables the evaluation of the influence of specific surface-properties on biological responses. To evaluate the effects of different surface chemistry on initial mechanisms of biomaterial induced coagulation, the surfaces were incubated with protein solution, human plasma, blood cell fractions or fresh heparinised human whole blood. Indicative hemocompatibility parameters were subsequently analysed focusing on protein adsorption, coagulation activation, contact activation (intrinsic/ enhancer pathway), impact of tissue factor (extrinsic/ activator pathway) and cellular systems (blood platelets and leukocytes).

Advances in biomaterials have enabled medical practitioners to replace diseased body parts or to assist in the healing process. In situations where a permanent biomaterial implant is used for a temporary application, additional surgeries are required to remove these implants once the healing process is complete, which increases medical costs and patient morbidity. Bio-absorbable materials dissolve and are metabolized by the body after the healing process is complete thereby negating additional surgeries for removal of implants. Magnesium alloys as novel bio-absorbable biomaterials, have attracted great attention recently because of their good mechanical properties, biocompatibility and corrosion rate in physiological environments. However, usage of Mg as biodegradable implant has been limited by its poor corrosion resistance in the physiological solutions. An optimal biodegradable implant must initially have slow degradation to ensure total mechanical integrity then degrade over time as the tissue heals. The current research focuses on surface modification of Mg alloy (MZC) by surface treatment and polymer coating in an effort to enhance the corrosion rate and biocompatibility. It is envisaged that the results obtained from this investigation would provide the academic community with insights for the utilization of bio-absorbable implants particularly for patients suffering from atherosclerosis. The alloying elements used in this study are zinc and calcium both of which are essential minerals in the human metabolic and healing processes. A hydrophobic biodegradable co-polymer, polyglycolic-co-caprolactone (PGCL), was used to coat the surface treated MZC to retard the initial degradation rate. Two surface treatments were selected: (a) acid etching and (b) anodization to produce different surface morphologies, roughness, surface energy, chemistry and hydrophobicity that are pivotal for PGCL adhesion onto the MZC. Additionally, analyses of biodegradation, biocompatibility, and mechanical integrity were performed in order to investigate the optimum surface modification process, suitable for biomaterial implants. The study concluded that anodization created better adhesion between the MZC and PGCL coating. Furthermore, PGCL coated anodized MZC exhibited lower corrosion rate, good mechanical integrity, and better biocompatibility as compared with acid etched.

Orientador: Francisco das Chagas Marques / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Fisica Gleb Wataghin / Made available in DSpace on 2018-08-16T08:31:55Z (GMT). No. of bitstreams: 1 Viana_GustavoAlexandre_D.pdf: 26050862 bytes, checksum: 8af75e89f5e6b6013343b0c988c3e7ee (MD5) Previous issue date: 2010 / Resumo: Ao longo desse projeto de doutorado, foi projetado e construído um sistema de deposição de filmes, livre de bombeamento (LB) de gás(es) no decorrer dos processos e capaz de realizar deposições em duas modalidades: ¿Sputtering¿ e PECVD (Plasma Enhanced Chemical Vapor Deposition). Amostras amorfas carbohidogenadas (a-C:H) do tipo diamantinas (DLC) e poliméricas (PLC) foram obtidas em deposições por PECVD, nas quais, variou-se o fluxo de gás metano (CH4 ¿ precursor). Com a redução dos fluxos, dentro das condições de deposição adotadas e da geometria de nosso sistema, são observados, para os filmes DLC (PLC), aumento da ordem de 83% (54%) para a taxa de deposição e queda de 44% (56%) no volume de CH4 consumido, para cada nm de filme depositado, porém, em razão da saturação da atmosfera de deposição por H2, não concomitante com o regime LB. Através de caracterizações optoeletrônicas, vibracionais e mecânicas, conforme se reduz o fluxo de CH4, observam-se comportamentos semelhantes em ambos os tipos de amostras depositadas para os valores do gap óptico e hidrogenação, sempre com as amostras do tipo PLC mais isolantes e hidrogenadas. Contudo, comportamentos distintos em relação ao índice de refração (n) e stress intrínseco são estabelecidos. Enquanto as amostras do tipo PLC apresentam-se praticamente não estressadas e com tendência de queda para o valor de , as do tipo DLC assistem ao crescimento de ambos os valores. Além disso, medidas de Raman no visível revelam aumentos para os valores da posição da banda G e razão ID/IG, conforme se reduz o fluxo de CH4, indicando aumento na proporção da razão sp2/sp3. Ainda para as amostras DLC, medidas de dureza mostraram ótimos resultados para este tipo de modalidade de deposição, chegando a valores de até ~20 GPa. Filmes amorfos não hidrogenados de carbono (a-C) foram depositados por ¿Sputtering ¿de um alvo de grafite em atmosferas de deposição compostas por Argônio (Ar) e Xenônio (Xe). Todas as deposições em atmosferas de Xe foram realizadas em regime LB, visando, com isso, além da economia no consumo de Xe, obter as condições de deposição que mais favorecessem sua incorporação por parte das matrizes de a-C. Da redução dos fluxos de Ar empregados nas deposições, os melhores resultados foram concomitantemente obtidos para o regime LB (diferente do que se observa em PECVD), onde um aumento de 70% na taxa de deposição foi acompanhado de uma queda de seis ordens de grandeza no volume de gás consumido para cada nm de filme depositado. Resultado este, excelente do ponto de vista de economia de gás(es). Assim como nas amostras depositadas por PECVD, nestas também foram realizadas caracterizações optoeletrônicas e mecânicas, as quais revelaram valores para o stress, gap óptico e n condizentes com amostras do tipo grafíticas (GLC). Medidas de efusão térmica, realizadas em amostras incorporadas de Xe, permitiram pela primeira vez, até onde sabemos, a determinação do coeficiente de difusão e da energia livre de difusão (~1.9 e V) para átomos de Xe aprisionados em uma matriz amorfa do tipo GLC. Procedimentos de ativação e posterior espectroscopia gama, conduzidos em amostras de a-C:Xe, confirmaram a capacidade de transmutação do isótopo estável 124Xe (abundância natural de 0.1%), via bombardeio de nêutrons térmicos e capturas eletrônicas, para o radionuclídeo 125I, muito utilizado em tratamentos anticancerígenos como o de próstata, por exemplo. Dessa forma, baseados nos resultados de ativação e detecção gama, na habilidade terapêutica do 125I e na bio/hemocompatibilidade dos filmes de a-C, nesse trabalho de doutorado, é proposto um modelo comercial para sementes clínicas, utilizadas em tratamentos localizados anticancerígenos denominados de Braquiterapia, baseadas em filmes amorfos de carbono incorporados do isótopo 124Xe (i.e., a-C:124Xe), com dose e atividade adequados para tal propósito / Abstract: In this PhD thesis a Sputtering and PECVD (Plasma Enhanced Chemical Vapor Deposition) deposition system, appropriated for deposition free of gas pumping along the procedure, was projected and built. Hydrogenated amorphous (a-C:H) with Diamond-Like carbon (DLC) and Polymer-Like carbon (PLC) structures were deposited by PECVD under different methane (CH4) flow rate. The properties of the films changes significantly as the CH4 flow rate decreases from high flow (~80 sccm) to zero flow (pumping free deposition). An increase in the deposition rate of the DLC (PLC) films by 83% (54%), accompanied by a fall of 44% (56%) of the CH4 volume consumed to deposited the films, was observed at CH4 flow rate of 3.9 sccm, compared to films deposited at high flow rate. For smaller CH4 flow rate, the deposition rate decreases due to H2 saturation of the deposition atmosphere. The optical gap (determined by uv-visible transmission spectroscopy) and hydrogen concentration (determined by FTIR) varies in a similar fashion for both series of films (DLC and PLC) as a function of CH4 flow rate. Electrical conductivity measurements revealed that the PLC films are always more insulating than the DLC films. The concentration of hydrogen (determined by FTIR) is much higher in PLC films. The behavior of the index of refraction and the stress as a function of CH4 flow rate, for both series of films, are quite different from each other. PLC films has very small stress and the index of refraction decreases as the CH4 decrease, while the opposite is observed for DLC films, which are very compressive stressed and the index of refraction increases in the same range. Visible Raman scattering, performed on the DLC films, shows an increase of the G peak position and ID/IG rate, as the CH4 decreases, indicating an increase in the sp2/sp3 ratio. Nanohardness measurements also show that the harder films (~20 GPa) are obtained at relatively low flow rate. Non-hydrogenated amorphous carbon films (a-C) were deposited by Sputtering a graphite target in argon (Ar) or xenon (Xe) atmosphere. Differently from the result observed in films deposited by PECVD, the highest deposition rate obtained by sputtering was under pumping free deposition (zero argon flow rate). In this case an increase of 70% in the deposition rate was obtained, accompanied by six order of magnitude drop of the gas consumption. All the depositions performed in Xe atmosphere were carried out in pumping free regime to reduce Xe consumption and also to determine the best deposition setup in order to acquire the higher incorporation on Xe into the a-C matrix. High concentration of xenon (3.6%) was obtained with an extremely low consumption of xenon gas. Optoelectronic and mechanical characterization were carried out in the films deposited by sputtering and revealed that their stress, index of refraction and optical gap are consistent with graphite-like carbon films (GLC). Thermal desorption spectroscopy, performed in Xe incorporated samples, allowed, for the first times, to the best of our knowledge, to determine the diffusion coefficient and the free diffusion energy (~19eV) of Xe atoms trapped into amorphous GLC matrix. Activation procedure followed by gamma counting spectroscopy, carried out in a-C:Xe films, confirm the isotopic transmutation ability of the stable 124Xe(0.1% of natural abundance), by thermal neutrons bombardment and electrons capture, to the radionuclide 125I, which is an element largely employed in anticancer treatment, like the prostate one, for example. Thus, based on the activation and gamma counting results, on the 125I therapeutic ability and the a-C hemo/biocompatibility, in this PhD thesis it is proposed a model for commercial clinical seeds, used in local anticancer treatment named Brachytherapy, based on the isotope 124Xe incorporated amorphous carbon film (i.e., a-C:124Xe), with appropriate dose and activity to this purpose / Doutorado / Física da Matéria Condensada / Doutor em Ciências

The surface of biomaterials can induce contacting blood to coagulate, similar to the response initiated by injured blood vessels to control blood loss. This poses a challenge to the use of biomaterials as the resulting coagulation can impair the performance of hemocompatible devices such as catheters, vascular stents and various extracorporeal tubings [1], what can moreover cause severe host reactions like embolism and infarction. Biomaterial induced coagulation processes limit the therapeutic use of medical products, what motivates the need for a better understanding of the basic mechanisms leading to this bio-incompatibility [2] in order to define modification strategies towards improved biomaterials [3]. Several approaches for the enhancement of hemocompatible surfaces include passive and active strategies for surface modifications. The materials’ chemical-physical properties like surface chemistry, wettability and polarity are parameters of passive modification approaches for improved hemocompatibility and are the focus of the present work. In the present study self assembled monolayers with different surface functionalities (-COOH, -OH, -CH3) were applied as well as two-component-layers with varying fractions of these, as they allow a defined graduation of surface wettability and charge. The ease of control over these parameters given by these model surfaces enables the evaluation of the influence of specific surface-properties on biological responses. To evaluate the effects of different surface chemistry on initial mechanisms of biomaterial induced coagulation, the surfaces were incubated with protein solution, human plasma, blood cell fractions or fresh heparinised human whole blood. Indicative hemocompatibility parameters were subsequently analysed focusing on protein adsorption, coagulation activation, contact activation (intrinsic/ enhancer pathway), impact of tissue factor (extrinsic/ activator pathway) and cellular systems (blood platelets and leukocytes).

Les limites des nanovecteurs commerciaux ou actuellement en développement ont motivé l’élaboration de nouvelles nanoparticules mésoporeuses de silice (MSNP), hybrides et multiphasées, pour le contrôle de la délivrance d’actifs à application théranostique. Ainsi, de nouvelles MSNP ont été conçues pour la pénétration intracellulaire (diamètre entre 30 et 60 nm, taille des pores de 2,8 nm). Afin de les rendre hémocompatibles et de contrôler la cinétique de délivrance de principes actifs encapsulés, ces MSNP ont été enrobées d’une bicouche lipidique (MSNP+@SLB-). La composition lipidique s’inspire des membranes asymétriques des globules rouges ciblés par la présente étude.La technologie MSNP+@SLB- ayant montré des limites avec une cinétique de libération trop élevée de la calcéine et trop lente de la rhodamine B, deux améliorations majeures ont été apportées :1- Le recouvrement des SLB par un nanogel d’alginate, permettant un excellent contrôle de la libération d’actifs.2- L’insertion de nanoparticules magnétiques dans le coeur des MSNP, déclenchant la libération de l’actif par hyperthermie.Ces nouvelles architectures de nanovecteurs permettent de moduler les cinétiques de délivrance d’actifs, renforçant et élargissant ainsi le champ d’applications des vecteurs silicés dans les domaines biomédical ( Voie orale et intraveineuse) et dermato-cosmétique (Voie topique). / The limitations of commercial nanovectors or currently under development have motivated the development of new hybrid and core shell mesoporous silica nanoparticles (MSNP) for the control of molecular delivery.Therefore, new MSNP were designed for intracellular penetration (diameter between 30 and 60 nm, pore size of 2.8 nm). In order to make them hemocompatible and to control the kinetics of delivery of encapsulated active ingredients, these MSNP were coated with a lipid bilayer (MSNP+@SLB-). The lipid composition is inspired by the asymmetric membranes of the red blood cells.Since the MSNP+@SLB- technology has shown some limitations associated to the release of payloads which can be too fast (in the case of calcein) or to slow (case of rhodamine B), two major improvements have been made:1- The coating of SLB by an alginate nanogel, allowing an excellent control of the release of active molecules.2- Insertion of magnetic nanoparticles in the MSNP core, triggering the release of the active ingredient by hyperthermia.These new nanovector architectures enable the fine tuning of active ingredient delivery kinetics, reinforcing and expanding the applications of silicated vectors in the fields of biomedicine (oral and intravenous) and dermato-cosmetics (topical).

The design of biomaterials, historically initiated and developed by physicians and engineers, in the last decades has slowly shifted toward a more biochemical based approach. For the replacement, repair and regeneration of tissues scientists are now focusing on materials that stimulate specific biological response at the molecular level. These biomaterials have already shown interesting applications in cell proliferation, differentiation, and extracellular matrix production and organization when the material modifications are designed to elicit specific interactions with cell integrins. In the present work we propose the application of this strategy for the development of blood-compatible materials. We first identified, in the coagulation cascade a key enzyme that constitute a valuable biological target for the development of anti-thrombogenic compounds. Piperazinyl-amide derivatives of N-alfa-(3-trifluoromethyl-benzenesulfonyl)-L-arginine were synthesized as graftable thrombin inhibitors. These inhibitors provided a spacer arm for surface grafting and a fluorine tag for XPS (X-ray photoelectron spectroscopy) detection. The possible disturbance of biological activity due to a variable spacer-arm fixed on the N-4 piperazinyl position was evaluated in vitro against human alfa-thrombin, in silico by molecular modelling and via X-ray diffraction study. Selected inhibitors, having inhibition potency in the mM range, were grafted on polyesters surface via wet chemistry and photochemical activation treatments. Wet chemistry surface grafting was performed by specific hydroxyl chain-ends activation and resulted in bioactive molecules fixation of 20-300pmol/cm2. The photochemical grafting was performed using a molecular clip providing an aromatic azide, for nitrene insertion into a polymer, and an activated ester for grafting of tag compounds. This grafting technique resulted in a dramatic increase in fixed bioactive signals (up to nmol/cm2). The material blood-compatibilization induced by the surface fixation of the inhibitors, was measured by a static blood clot weight measurement test. The wet chemistry grafting technique resulted in moderate blood-compatibilization while by the photochemical grafting method important decrease in surface blood clot formation was observed. In the latter case, the blood response to material contact was found to be strongly affected by the polyester surface photo-degradation induced by the activation treatment.

The design of biomaterials, historically initiated and developed by physicians and engineers, in the last decades has slowly shifted toward a more biochemical based approach. For the replacement, repair and regeneration of tissues scientists are now focusing on materials that stimulate specific biological response at the molecular level. These biomaterials have already shown interesting applications in cell proliferation, differentiation, and extracellular matrix production and organization when the material modifications are designed to elicit specific interactions with cell integrins. In the present work we propose the application of this strategy for the development of blood-compatible materials. We first identified, in the coagulation cascade a key enzyme that constitute a valuable biological target for the development of anti-thrombogenic compounds. Piperazinyl-amide derivatives of N-alfa-(3-trifluoromethyl-benzenesulfonyl)-L-arginine were synthesized as graftable thrombin inhibitors. These inhibitors provided a spacer arm for surface grafting and a fluorine tag for XPS (X-ray photoelectron spectroscopy) detection. The possible disturbance of biological activity due to a variable spacer-arm fixed on the N-4 piperazinyl position was evaluated in vitro against human alfa-thrombin, in silico by molecular modelling and via X-ray diffraction study. Selected inhibitors, having inhibition potency in the mM range, were grafted on polyesters surface via wet chemistry and photochemical activation treatments. Wet chemistry surface grafting was performed by specific hydroxyl chain-ends activation and resulted in bioactive molecules fixation of 20-300pmol/cm2. The photochemical grafting was performed using a molecular clip providing an aromatic azide, for nitrene insertion into a polymer, and an activated ester for grafting of tag compounds. This grafting technique resulted in a dramatic increase in fixed bioactive signals (up to nmol/cm2). The material blood-compatibilization induced by the surface fixation of the inhibitors, was measured by a static blood clot weight measurement test. The wet chemistry grafting technique resulted in moderate blood-compatibilization while by the photochemical grafting method important decrease in surface blood clot formation was observed. In the latter case, the blood response to material contact was found to be strongly affected by the polyester surface photo-degradation induced by the activation treatment.

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