Dissertations / Theses on the topic 'Non-biodegradable'

Different structures of non-viral cationic polymer delivery vehicles, including charge center type, molecular weight and degradability, could significantly affect toxicity, release of nucleic acid and transfection efficiency. Poly(glycoamidoamine)s (PGAAs) contained different carbohydrate and secondary amine moieties and showed high transfection efficiency to different cell lines in a nontoxic manner. The "proton sponge hypothesis" has attempted to relate the buffering capacity to endosomal release of polyethylenimine (PEI) based polyplexes, which could contribute to high transfection efficiency. Secondary amine structures rendered PGAAs buffering capacity around physiological pH. To test the feasibility of the mechanism for PGAAs, new no buffering capacity guanidine or methylguanidine containing poly(glycoamidoguanidine)s (PGAGs) were synthesized. PGAGs formed stable polyplexes with pDNA from N/P (# secondary amine or guanidine group on polymer backbone / # phosphate group on pDNA backbone) ratio 3. PGAG based polyplexes expressed low cytotoxicity and were internalized by 90% of cells at N/P 25. Furthermore, two PGAG based polyplexes showed higher transfection efficiency from N/P 5 to 30 than their PGAA based analogs. These data suggested the low transfection could be due to the difficulties to release pDNA from polyplexes; also, the "proton sponge theory" could not explain the higher transfection efficiency by some PGAGs. Degradation of delivery vehicles could potentially release pDNA in cells and increase transfection efficiency. PGAAs degraded rapidly at physiological conditions and the proposed mechanism was amide hydrolysis. Typically, amide groups are stable and hydrolyze slowly in absence of enzyme. Different models mimicking PGAAs were synthesized to study the fast hydrolysis. Amide groups showed asymmetric hydrolysis. Different hydrolysis behaviors suggested neighboring group participation of two terminal groups to induce rapid amide hydrolysis. These new models could potentially be used to design new polymer delivery vehicles with various degradation profiles.
Master of Science

Pharmaceuticals in the aquatic environment is an emerging issue and the risks they pose are mostly unknown. They are used in large amounts throughout the world and can enter the environment, as the active metabolite or unmetabolised, through excretion by people and improper disposal. As these drugs are designed to have specific biological effects in a specific organism (as well as sometimes having other non-specific side effects), their potential to cause effects within the environment is great. Clofibric acid (the major metabolite of the lipid lowering drug, Clofibrate) is non-biodegradable, highly motile, very persistent and frequently detected at μg/I levels in the environment. I studied possible effects of clofibric acid in fish, using different experimental approaches and endpoints. The studies involve two different species, and for one of these species, fish at different stages of development. The chapters within this thesis have presented the first evidence (albeit preliminary) of clofibric acid having effects on both adult and embryo fish. When fathead minnow embryos were exposed to clofibric acid, the effects seen included changes in the eggshell, time to hatch, hatchability, mortality and viability. Adult fathead minnow were similarly exposed and significant effects on specific parameters were also observed. These included effects on lipid metabolism, steroidogenesis and spermatogenesis - thought to be via cholesterol transport - as well as significant effects on the expression of several genes involved in lipid metabolism and detoxification. Exposure of juvenile (sexually undifferentiated) bream also found significant differences in some endpoints. Other results suggested, less pronounced effects of clofibric acid on some other parameters. The results from this research show that there are effects of clofibric acid in pathways which were not only unexpected in fish (for example, steroidogenesis, spermatogenesis and gene expression), but also at concentrations below those previously shown to have any biological effects on fish. These effects indicate that clofibric acid may potentially have an impact on fish fecundity, and even more worryingly, on human health for those people prescribed it.

Reports from various institutions claim that garbage management in Rwanda has had diverse effects on both the natural environment and human society. Such claims prompted for an exploratory study to find out an optimal system to handle solid waste in Kigali City. The study considered a literature review and primary data from 400 randomly selected citizens. They were surveyed about their opinions on which system they perceived to be the optimal to handle garbage in Kigali City. The computer software Web-Hipre was used to analyze data on the three systems considered to handle solid waste in Rwanda: briquetting, composting, and incineration.The results indicate briquetting as the optimal alternative to handle solid waste from homesteads and workplaces of Kigali City. Briquetting considers production of solid fuels that may reduce destruction of forests for fuel. Other major reasons for briquetting, highlighted by respondents, include improved kitchen hygiene and sanitation and replacement of charcoal for a less dusty fuel. Economic factors governed surveyed participants to prioritise briquetting system to handle solid waste in Kigali. Composting may be considered for transforming organic materials into mulch to support farming activities in rural areas as well as gardening in the towns. However, a centralised incineration system is presently not suitable. The private sector has so far not fully been engaged in the transformation of solid waste into bioenergy in Rwanda.

Reports from various institutions claim that garbage management in Rwanda has had diverse effectson both the natural environment and human society. Such claims prompted for an exploratory study to find outan optimal system to handle solid waste in Kigali City.The study considered a literature review and primary data from 400 randomly selected citizens. They weresurveyed about their opinions on which system they perceived to be the optimal to handle garbage in KigaliCity. The computer software Web-Hipre was used to analyze data on the three systems considered to handlesolid waste in Rwanda: briquetting, composting, and incineration.The results indicate briquetting as the optimal alternative to handle solid waste from homesteads and workplacesof Kigali City. Briquetting considers production of solid fuels that may reduce destruction of forests for fuel.Other major reasons for briquetting, highlighted by respondents, include improved kitchen hygiene andsanitation and replacement of charcoal for a less dusty fuel.Economic factors governed surveyed participants to prioritise briquetting system to handle solid waste in Kigali.Composting may be considered for transforming organic materials into mulch to support farming activities inrural areas as well as gardening in the towns. However, a centralised incineration system is presently notsuitable. The private sector has so far not fully been engaged in the transformation of solid waste into bioenergyin Rwanda.

La pollution plastique océanique est l’une préoccupation majeure de notre siècle, avec plusieurs millions de tonnes de plastique déversées dans l'océan chaque année qui menacent la santé des écosystèmes. Les effets des plastiques ont été identifiés à tous les niveaux de la chaîne trophique, du zooplancton à la mégafaune, mais leurs effets sur la vie des microorganismes et sur leur rôle crucial dans le fonctionnement de l'écosystème océanique restent méconnus. L'objectif de cette thèse était d'étudier l'écotoxicité des plastiques en milieu marin. La première question traitée était : dans quelle mesure l'abondance, la diversité et l'activité de la vie bactérienne se développant sur le plastique, nommée «plastisphère», sont influencées par les propriétés chimiques du polymère et les changements environnementaux (chapitre 2)? Ce point a été abordé en immergeant pendant 2 mois dans l'eau de mer du Polyéthylène (PE), de l’acide polylactide (PLA) ainsi que du verre comme témoin, sous différentes formes : méso-débris (18 mm de diamètre), grands microplastiques (LMP; 3 mm de diamètre), et petits microplastiques (SMP; de 100 µm de diamètre de formes sphériques et irrégulières). Nous avons constaté que la composition chimique du plastique, les phases successives de formation du biofilm et les interactions phytoplancton-bactéries étaient des facteurs déterminants de l'abondance, de la diversité et de l'activité de la plastisphère a contrario de la taille et à la forme du matériau.La deuxième question traitée était : le microplastique (polystyrène PS; 50-100 µm; trois concentrations) ainsi que leur biofilm mature seraient-ils toxiques pour le filtre-filtreur marin Branchiostoma lanceolatum et dans quelles mesures la plastisphère peut-elle influencer cette toxicité (chapitre 3)? Nous avons utilisé un large éventail de techniques complémentaires pour suivre l'ingestion des microplastiques (quantification microscopique) à l’origine d’une potentielle modification du microbiote intestinal de l’hôte (séquençage 16S rRNA Illumina Miseq). La réponse physiologique de l’hôte a également été suivie au travers de l’expression génique du système immunitaire, du stress oxydatif et de l’apoptose (Nanostring) ainsi que par histopathologie ( La microscopie électronique à transmission). Aucune toxicité évidente n'a été observée, alors que les microplastiques pourraient être un vecteur de modification du microbiome intestinal, et qu’une plus grande différenciation des cellules a été observée au niveau des tissus intestinaux. La troisième question traitée était: Existe-t-il des alternatives aux microbilles pétrochimiques conventionnels utilisées en cosmétique biodégradables en milieu marin? (Chapitre 4). Nous avons utilisé une approche multidisciplinaire pour suivre les 4 étapes de biodégradation dont la 1/biodétérioration (granulométrie, gravimétrie et spectroscopie FTIR), 2/la biofragmentation (chromatographie d'exclusion de taille, résonance magnétique nucléaire 1H et spectrométrie de masse à haute résolution), 3/la bioassimilation et 4/la minéralisation (résonance magnétique nucléaire 1H et mesures de l'oxygène) sur différentes formes de microbilles en présence de bactéries marines. Après 60 jours d’incubation, nos résultats ont permis d’identifier des microbilles de polyhydroxybutyrate-co-hydroxyvalérate (PHBV) ou de riz et dans une moindre mesure de polycaprolactone (PCL) et d'abricot comme alternatives aux microplastiques conventionnels, en PE ou en polyméthacrylate de méthyle (PMMA) non biodégradés dans nos conditions. Fait remarquable, le PLA biosourcé n'était pas biodégradable, mais le PCL pétrochimique était biodégradable dans nos conditions marines
Oceanic plastic pollution is of major concern, with several million tons of plastic dumped in the ocean every year that are causing health threat to marine creatures. Impacts have been found at all the trophic chain levels from the zooplankton to the megafauna, but little is known on its impact on the microbial life and its crucial role in the oceanic ecosystem functioning. The objective of this thesis was to study the ecotoxicity of plastics in the marine environment. The first handled question was: how much the abundance, diversity and activity of bacterial life growing on plastic, i.e. the ‘plastisphere’ are driven by the chemical properties of the polymer and the environmental changes (Chapter 2)? Polyethylene (PE) and polylactide acid (PLA) together with glass controls in the forms of meso-debris (18mm diameter) and large-microplastics (LMP; 3mm diameter), as well as small-microplastics (SMP; of 100 m diameter with spherical and irregular shapes) were immerged during 2 months in seawater. We found that the plastic chemical composition, the successive phases of biofilm formation and the phytoplankton-bacteria interactions were more important factors driving the abundance, diversity and activity of the plastisphere as compared to material size and shape. The second handled question was: would the microplastic (polystyrene PS; 50-100 µm; three concentrations) together with their mature biofilm be toxic for the marine filter-feeder Branchiostoma lanceolatum and how much the plastisphere can influence this toxicity (Chapter 3)? We used a large set of complementary techniques to follow the microplastic ingestion (microscopy quantification) and the modification of the gut microbiota (16S rRNA Illumina Miseq sequencing), the gene expression of immune system, oxidative stress and apoptosis (Nanostring) and also histopathology (transmission electron microscopy). No obvious toxicity was observed, while microplastics could be a vector for bacteria to the gut microbiome, can induce more goblet cell differentiation and can surprisingly have a positive effect by supplying nutrients to amphioxus in the form of bacteria and diatoms from the plastisphere. The third handled question was: how much the conventional petroleum-based microbeads classically used in cosmetics can be substituted by other polymers for their biodegradability by the plastisphere in marine environment? (Chapter 4). We used complementary techniques to follow the 4 biodegradation steps including biodeterioration (granulometry, gravimetry and FTIR spectroscopy), biofragmentation (size exclusion chromatography, 1H nuclear magnetic resonance and high-resolution mass spectrometry), bioassimilation and mineralization (1H nuclear magnetic resonance and oxygen measurements). We concluded that microbeads made of polyhydroxybutyrate-co-hydroxyvalerate (PHBV) or rice and in a lesser extend polycaprolactone (PCL) and apricot were good candidates for substitution of conventional microplastics, classically made of PE or polymethyl methacrylate (PMMA) that were not biodegraded under our conditions. Interestingly, the biobased PLA was not biodegradable but the petroleum-based PCL was biodegradable under our marine conditions

M.Tech. (Department of Chemistry, Faculty of Applied and Computer Sciences), Vaal University of Technology
Water contaminated with non-biodegradable organics is becoming increasing problematic as it has a hazardous effect on human health and the aquatic environment. Therefore, the removal of organic contaminants is of importance and an active heterogeneous Fenton catalyst is thus required. The literature indicates that a bimetallic oxide Fenton catalyst is more active than an iron oxide catalyst. This study focused on increasing the activity of iron-based Fenton catalysts with the addition of transition metals such as manganese, cobalt and copper and optimizing the preparation method. In this study, bimetallic oxide (Fe-Cu, Fe-Mn, Fe-Co) and monometallic oxide (Fe, Cu, Mn,Co) catalysts supported on silica SiO2 where prepared by incipient wetness impregnation. The total metal oxide contents were kept constant. The catalysts where calcined in two different ways, in a conventional oven and in a microwave. These catalysts were characterized with XRD, XPS and CV and were tested for the degradation of methylene blue dye at 27°C. The catalysts calcined in a microwave oven had a higher catalytic activity than those prepared in a conventional oven. The bimetallic oxide catalysts outperformed the mono- metallic oxide catalysts in the degradation of methylene blue. The Fe2MnOx prepared by microwave energy were the most active catalyst yielding the highest percentage of degradation of methylene blue dye (89.6%) after 60 minutes. The relative amounts of manganese and iron oxide were varied while keeping the total metal content in the catalyst the same. The optimum ratio of Fe to Mn was 1:7.5 since it yielded the most active catalyst. A 96.6 % removal of methylene blue was achieved after 1 hour of degradation. Lastly this ratio 1Fe:7.5Mn was prepared by varying different microwave power (600, 700 and 800 W) and irradiation time (10, 20 and 30 min). The optimum microwave power and irradiation time was 800W and 10 min with the methylene blue percentage removal of 96.6 % after 1 hour of degradation.

Les fibres naturelles ont récemment attiré l'attention des scientifiques en raison de leurs propriétés : faible coût, faible densité, renouvelables, biodégradables et non abrasives. Dans cette étude, trois types de fibres de bambou sont étudiées. La modification chimique des fibres par la soude est utilisée pour enlever l'hémicellulose et la lignine. Puis, la surface de la fibre est modifiée par acétylation ou silane avant élaboration de composites PP. Les propriétés mécaniques des composites augmentent avec le diamètre des fibres et avec l'utilisation d'un agent d'ensimage. Des mélanges amidon/PVA/plastifiant/agent de couplage sont également étudiés. Les composites préparés par réticulation avec l'acide citrique ont d'excellentes propriétés mécaniques. La résistance à la traction et la déformation à rupture de ces composite augmentent avec la teneur en PVA. La présence d'argile et de fibres ont toutes deux un effet considérable sur les propriétés mécaniques des composites
Natural fibers have recently attracted the attention of scientists because of their properties of low-cost, low density, renewable, biodegradable and nonabrasive. In this study, three types of bamboo fibers are prepared. Chemical modification of fibers by alkali is used to remove hemicellulose and lignin. Then, fiber surface is modified by acetylation and silane before processing composite materials with polypropylene. As expected, the mechanical properties of the composites increase with the average fibre diameter. Tensile strength and Young's modulus increase when using a coupling agent. Starch/PVA blends are also prepared with glycerol and water as plasticizer. The composite prepared by citric acid crosslinking has excellent mechanical properties. Tensile strength and elongation at break of starch/ PVA composite increase with the content of PVA. The presence of clay and fiber are both found to have considerable effect on the mechanical properties of the composites

Tese de doutoramento em Programa Inter-Universitário de Doutoramento em Matemática, apresentada ao Departamento de Matemática da Faculdade de Ciências e Tecnologia da Universidade de Coimbra
Mathematical modeling and numerical simulation of cardiovascular drug delivery systems have become an effective tool to gain deeper insights in the phar macokinetics of therapeutic agents in cardiovascular diseases like atherosclerosis. Drug Eluting Stents (DES) which are tiny expandable mesh tubes coated by a polymer with dispersed drug, represent a major advance in the treatment of ob- structed artery diseases. The main objective of this thesis is to study a mathematical model that sim- ulates ”in vivo” drug delivery from a biodegradable DES. To study the complete problem of penetration of therapeutic agent from DES into the arterial wall, we progressively address more complex models. The first model, presented in Chapter 2, will describe with detail, in a simple two dimensional geometry, the biodegradation of polylactic acid (PLA), a material of choice in the design of DES, that degrades due to the penetration of plasma that breaks the polymer chains and reduces its molecular weight. When drug diffuses from a polymer into a viscoelastic arterial wall, it is observed that the process can not be completely described by Fick’s law of diffusion which was proposed by Adolf Fick in 1855. The reason lies in the fact that as drug diffuses into the arterial wall, it causes a deformation which induces a stress driven diffusion that act as a barrier to the drug penetration. Thus a modified flux should be considered, resulting from a sum of the Fickian flux and a non-Fickian flux. To take into consideration this non-Fickian flux, we add a degree of complexity to the first model, by introducing in Chapter 3 the stress response of the arterial wall. It is a memory effect established from Maxwell-Wiechert model or Fung’s quasilinear viscoelastic model. To obtain a more realistic model of drug pharmacokinetics, the reversible na- ture of binding, between the agent and immobilized sites in the arterial wall, is considered in Chapter 4. The behavior of different families of drugs is compared. Theoretical results concerning qualitative properties of the solutions and sta- bility of the models are presented along the dissertation. From the numerical viewpoint some aspects of clinical importance such as the influence of elastic mod- ulus of the arterial wall, the effect of biodegradation of PLA, the permeability of the stent coating as well as the binding rates in the arterial wall will be addressed in this thesis. A software package, to simulate the models in this dissertation, has been de-veloped using freeFEM++ . A modelação matemática e a simulação numérica do comportamento de sistemas de libertação controlada de fármacos constituem um instrumento entral na compreensão da farmacocinética de agentes terapêuticos nas doenças cardiovasculares, como por exemplo a aterosclerose. Os ”stents” com libertação controlada de fármaco1, que são tubos metálicos revestidos por um políımero que contem um fármaco disperso, constituem um tratamento de eleição em caso de obstrução de vasos. O objectivo central desta tese é o estudo analítico e numérico de um modelo matemático que descreva a libertação de fármacos ”in vivo”, a partir de um ”stent” com revestimento biodegradável. Para tal apresentamos ao longo da dissertação modelos progressivamente mais complexos, que culminam num sistema que descreve a biodegradação do polímero mas também propriedades dos tecidos vasculares como a viscoelasticidade e a ocorrência de afinidades entre o fármaco e o tecido vascular. O primeiro modelo que estudamos, no Capítulo 2, descreve com detalhe a influência da biodegradação do ácido poliláctico, que é um dos políımeros mais usados no revestimento de stents. A degradação ocorre devido à penetração do plasma no stent com a consequente quebra das cadeias do políımero e a reducão do seu peso molecular. Quando o fármaco se difunde na parede vascular, que é viscoelástica, o processo não pode ser completamente descrito pela Lei de Fick, proposta por Adolf Fick em 1855. A razão reside no facto de o fármaco, ao difundir-se na parede vascular, causar uma deformação, que induz uma resposta do polímero sob a forma de uma resistência à penetração do agente terapêutico. No Capítulo 3 o fluxo Fickiano, considerado no modelo do Capítulo 2, é então modificado, pela introduçãoo de um ”anti-fluxo” de origem viscoelástica.Para obter uma descriçãoo mais realista da farmacocinética do agente terapêutico na parede do vaso incluímos, no Capítulo 4, a afinidade química entre o agente e o tecido vivo. O comportamento de fármacos hidrofílicos e hidrofóbicos é analisado. Sãoo apresentados nesta dissertacão resultados teóricos relativos às propriedades qualitativas das soluções s e à estabilidade dos modelos estudados. Do ponto de vista numérico são discutidos diferentes aspectos de importância clínica, como a influência do módulo de Young da parede vascular, as propriedades de degradação, a permeabilidade do revestimento polimérico e a afinidade do fármaco com a parede vascular. Foi desenvolvida uma aplicação computacional, utilizando o ”software” de livre acesso freeFEM++, para simular o comportamento dos modelos estudados nesta tese.
FCT - SFRH/BD/51167/2010

Dissertação de mestrado integrado em Engenharia Biomédica (área de especialização em Engenharia Clínica)
Osteomyelitis is a frequent complication of diabetic foot ulcers and/or diabetic foot infection. It is defined as an infection of bone tissue and it is an aggravated condition in diabetic patient due to their poor blood flow and elevated blood glucose levels, which can increase biofilm formation. In general, osteomyelitis cannot be eradicated merely by intravenous administration of antibiotics. A successful treatment will include a combination of surgical procedures, usually surgical debridement of dead infected tissue and local antibiotic therapy. Non-degradable delivery devices are currently used for local antibiotic administration. The poly(methylmethacrylate) (PMMA) is widely used to develop gentamicin-loaded beads that are implanted on the local of infection. Even though these beads are routinely used to treat osteomyelitis, they present several disadvantages, including the requirement for a second surgery to remove the beads after treatment. Hence, the use of biodegradable devices for antibiotic delivery in osteomyelitis is a very attractive alternative. The poly(trimethylene carbonate) (PTMC) is an enzymatically biodegradable polymer that does not produce acidic degradation products. In the current thesis, the suitability of PTMC to function as an antibiotic delivery device for the local treatment of osteomyelitis was explored. Gentamicin-loaded PTMC beads were produced and their release kinetics was assessed. The inhibition of biofilm formation was also evaluated for these beads and compared with the commercially available PMMA Septopal® beads. Additionally, the glucose influence in biofilm growth was also studied, namely medium with and without 2.6 g/L concentration of glucose was used to grow the biofilm The results showed that the mass of biofilm (Enterobacter cloacae, Staphylococcus aureus) increased when glucose was present in the culture medium, which may explain the difficulties that are observed in the treatment of diabetic foot osteomyelitis. The antibiotic release profile and inhibition of biofilm formation by the PTMC beads was found to be similar to the PMMA beads. Therefore, PTMC seems a promising biodegradable carrier to be used in the local treatment of osteomyelitis.
A osteomielite é uma complicação frequente em úlceras e/ou infeção do pé diabético. É definida como uma infecção do tecido ósseo, agravada em pacientes diabéticos devido ao baixo fluxo sanguíneo e elevado nível de glucose no sangue, o que pode contribuir para a formação de biofilme. Em geral, a osteomielite não pode ser erradicada meramente com administração intravenosa de antibióticos. Um tratamento bem-sucedido inclui uma combinação de procedimentos cirúrgicos, geralmente remoção cirúrgica do tecido infectado e morto, seguido de terapia antibiótica local. Dispositivos de administração nãobiodegradáveis são actualmente utilizados para a administração de antibióticos no local infectado. O poli (metacrilato de metilo) (PMMA) é amplamente utilizado para desenvolver sistemas de libertação controlada de antibióticos, e estes são implantados no local infetado. Embora as partículas de PMMA sejam utilizadas com frequência no tratamento da osteomielite, estas apresentam várias desvantagens, incluindo a exigência de uma segunda cirurgia para as remover, após o tratamento. A utilização de dispositivos biodegradáveis para a libertação de antibióticos no tratamento da osteomielite é uma alternativa muito atraente. O poli (carbonato de trimetileno) (PTMC) é um polímero enzimaticamente biodegradável que não produz produtos de degradação ácidos. No presente trabalho foi explorada a adequação de PTMC para funcionar como um dispositivo de administração de antibiótico para o tratamento local da osteomielite. Foram produzidas partículas de PTMC carregadas com gentamicina e a cinética de libertação do antibiótico foi avaliada. Adicionalmente, a inibição da formação de biofilme foi estudada e comparada com as partículas de PMMA Septopal® comercialmente disponíveis. Além disso, a influência da glucose no crescimento de biofilme também fez parte deste estudo e por conseguinte, desenvolveu-se um biofilme em meio sem e com glucose com uma concentração de 2.6 g/L Os resultados mostraram que a massa de biofilme (Enterobacter cloacae, Staphylococcus aureus) aumentou na presença de glucose no meio de cultura, o que pode explicar a dificuldade observada no tratamento da osteomielite do pé diabético. O perfil de libertação do antibiótico e a inibição da formação de biofilme para as partículas de PTMC foi semelhante ao encontrado para as partículas de PMMA. Nesse sentido, as partículas de PTMC parecem ser um transportador biodegradável promissor no tratamento local de osteomielite.

In this work, biodegradable branched triacrylate/amine polycationic polymers (TAPPs) were synthesized from different amine and triacrylate monomers by Michael addition polymerization and incorporated into a composite scaffold to evaluate these polymers in a bone tissue engineering system. The effects of the hydrophilic spacer lengths in the polymer on characteristics which are important for gene delivery were evaluated by varying the triacrylate monomer used in the synthesis. The results demonstrated that hydrophilic spacers can be incorporated into polycationic polymers to reduce their cytotoxicity and enhance the degradability. The effects of amine basicities in the polymer on characteristics which are important for gene delivery were also evaluated by varying the amine monomers used in the synthesis. The results indicated that polycationic polymers with amines that dissociate above pH 7.4, which are available as positively charged groups for plasmid DNA (pDNA) complexation at pH 7.4, can be synthesized to produce stable polyplexes with increased zeta potential and decreased hydrodynamic size that efficiently transfect cells. TAPP/pDNA polyplexes were then incorporated into a composite containing gelatin microparticles (GMPs) and a porous poly(propylene fumarate) scaffold. The release of pDNA in vitro was not affected by the crosslinking density of the GMPs but depended, instead, on the degradation rates of the TAPPs. Besides the initial burst release of polyplexes not bounded to the GMPs and the minimal release of pDNA through diffusion and dissociation from the GMPs, the pDNA was likely released as naked pDNA or in an incomplete polyplex as fragments of the polymer had to degrade to release the pDNA. The results indicated that polymeric vectors with a lower degradation rate can prolong the release of pDNA from the composite scaffold. Composite scaffolds loaded with TAPP/pDNA polyplexes may not have delivered enough intact polyplexes, as enhanced bone formation was not observed in a critical-size rat cranial defect at 12 weeks postimplantation compared to those loaded with naked pDNA. A gene delivery system consisting of biodegradable polycationic polymers should be designed to release the pDNA in an intact polyplex form.

碩士
國立中正大學
化學所
96
Gene therapy is an experimental technique that uses genes to treat or prevent disease. This technique may allow doctors to treat a disorder by inserting a gene into a patient’s cells instead of using drugs or surgery. The goal of this project is to design and synthesize a biodegradable cationic poly( urethane-co-ethylenimine ) with low cytotoxicity and high transfection efficiency. The polycation / DNA complex not only can protect the DNA from nuclease degradation, but also has a nanoscale size small enough to enter the cell via endocytosis. The results revealed that PU-l PEI, PU-Gly-l PEI, PU-hPEI and PU-Gly-hpei could bind with plasmid DNA and yield positively charged complexes with a size required for transfection. The PU-hPEI, PU-Gly-hPEI /DNA complexes were able to transfect COS-7 cells in vitro with an efficiency comparable to a well-known gene carrier PEI. In this article, PU-hPEI, PU-Gly-hPEI seemed to be novel cationic polyurethanes for gene delivery and an interesting candidate for further study.

碩士
臺北醫學大學
口腔復健醫學研究所
92
By testing the possibility of growing periodontal ligament cells on the poly L-lactic acid and anionized titanium bone screw, which can help us learn about the biocompatibility of tested biomaterials. If we can use these biomaterial as medias for PDL cell repopulation and forming new attachment, perhaps we can follow our knowledge about tissue engineering and develop a new way to use these biomaterial. Nine New Zealand white rabbits ,average three kilogram, were divided into three groups. They were randomly assigned by 4,8and 12 weeks experiment period. One 8mm x 2mmPLLA and one 6mm x 1.3mm anionized titanium screw were placed on each side of lower jaw of each rabbit. The screws were implanted and perforating the root of incisor so as to touch the PDL directly. The PLLA screw was assigned as test and anionized titanium screws as control. Totally 18 PLLA and 18 anionized titanium screws were used in this experiment. At the end of each group rabbits were sacrificed and the biopsy block samples were collected and prepared with HE stain for light microscopic histomorphlogical evaluation. One of the same pack of PLLA and anionized titanium screws were also used for SEM evaluation for its surface characteristic which might affect the tissue response. The SEM showed even distributed micro-porosity of the anionized titanium screw. A wide variation on the PLLA, smooth on the convex of the screw and micro-groove and crack line on the concave of the screw. The histology showed PDL cells can repopulate on both PLLA and titanium screw at four week samples. The direction of PDL fiber does not totally parallel the screw surface but focus constricted to the most concavity of the screw. The direct bone screw contact can be seen and the density of surrounding bone and the amount of direct bone screw contact increasing by the time from four to twelve weeks period. This study shows the possibility of the repopulation and forming new attachment of PDL cell and possible functional non-paralleled fiber alignment on both PLLA and anionized titanium screw surface. With this cell and tissue conducting pattern, we might be able to develop new biomaterial or new clinical application without following the principle of guided tissue regeneration.

Conventional urea-based moulding compounds for investment casting patterns are manufactured using a slow “cooking” process. Nowadays in industrial processes the use of a faster process is highly recommended to increase throughput levels. At the same time, for quality control purposes, the requirements of an investment caster must be met. This study is therefore focused on:

• Finding the appropriate conventional process and conditions to prepare urea-based investment casting moulding compounds.
• Optimising the composition variables to meet the mechanical, thermal, surface, flow and cost properties needed in investment casting.
• Characterising the moulding compounds to meet the requirements of an investment caster by comparing them with an industrial, “cooked” urea-based compound.

Polyvinyl alcohol (PVOH) and ethylene vinyl acetate (EVA) urea-based moulding compounds were prepared using a two-roll mill and a conventional extrusion processes respectively. It was possible to injection mould PVOH urea-based moulding compounds with a urea content of up to 90 wt % which had been compounded using a two-roll mill. Using the conventional extrusion process, it was also possible to compound and injection mould EVA urea-based moulding compounds containing up to 70 wt % urea. The effects on composition variables on the properties of the moulding compound were studied and compared to those of the existing “cooked” urea-based moulding compound (Benchmark). The mechanical properties were characterised using the three-point bending test and Charpy impact test. The thermal properties were determined using simultaneous differential thermal analysis and thermogravimetric analysis (SDTA/TGA) and differential scanning calorimeter (DSC). The thermo-mechanical and visco-elastic properties were determined using a dynamic mechanical analyser. A scanning electron microscope was used to study the surface texture of the mouldings. The EVA urea-based moulding compounds showed two endothermic melting peaks and multiple exothermic crystallisation peaks in the DSC curves. The peak at ca. 55 - 66°C corresponds to the melting of the wax/EVA blend, while the large peak at 130 - 132°C corresponds to the melting of the urea. The DSC heating curve of the PVOH urea-based moulding compounds showed two endothermic peaks. The small peak corresponds to the melting of the wax, while the large peak corresponds to the melting of the urea/PVOH blend. PVOH urea-based moulding compound had better mechanical properties than the industrial benchmark. The mechanical properties of the EVA urea-based compound were generally lower. The effect of the wax and polymer content on the mechanical properties was as follows:

• Increasing polymer content produced weaker but tougher moulding compounds.
• Increasing wax content improved the strength and stiffness but gave compounds that were less tough.
• Two-way Analysis of Variance (ANOVA) indicated significant polymer-wax interactions.

The urea content determined the stiffness (elastic modulus) of the compounds. PVOH mouldings had superior stiffness compared with the EVA and cooked urea-based mouldings. The Dynamic mechanical analysis (DMA) results confirmed the result obtained from the modulus of elasticity determination in the three-point bending test. The impact strength increased with an increase in polymer content and reduced with an increase in wax content. The linear thermal expansion coefficient decreased as the urea content was increased. Measured values (100 to 156x10-6°C) were comparable to those of the benchmark. The cooked urea-based moulding compound had the lowest melt viscosity at 110°C, as indicated by its melt flow index (MFI). Fluidity increased with the polymer content. The thermo gravimetric analysis (TGA) results confirmed that both the PVOH and EVA urea-based moulding compounds decomposed readily and left less than 1 wt % ash after combustion. From the SEM results apparent surface roughness appeared to increase with wax content. The EVA urea-based moulding compound had an irregular surface texture. Based on the criteria of cost-effectiveness and environmental friendliness, the synthesis of PVOH urea-based patterns is preferable. The use of a conventional extrusion process to prepare PVOH urea-based patterns is recommended.
Thesis (PhD)--University of Pretoria, 2011.
Chemical Engineering
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