Ce mémoire présente une exploration des polymères à empreintes moléculaires (MIP) comme outils d’une libération contrôlée de bioactifs olfactifs ou pour le criblage/préselection de composés à activité antivirales ou anti-tumorales sur le site actif d’une enzyme. La première partie est une étude de la complexation de la vanilline sur des billes polymériques sphériques en vue d’une libération contrôlée (pH, salinité, …). Ces études portent sur les caractéristiques de l'absorption et la libération de la molécule d'intérêt dans le milieu aqueux sur les microsphères fonctionnalisées fourni par Merck ESTAPOR® Microsphères. Nous avons ensuite synthétisé divers MIP de vanilline au format monolithique. Plusieurs stratégies d’impression ont été étudiées: non covalente, covalente et semi-covalente. La composition du MIP préparé dans chaque approche a été optimisée pour obtenir les meilleures propriétés et performances. L'affinité, la sélectivité et la capacité du MIP ont été déterminées. Les MIPs ont été évalués par extraction en phase solide (SPE) d'analogues structuraux de la vanilline dans des échantillons naturels (extrait de vanille, vin). La deuxième partie de ce mémoire concerne l’évaluation de MIPs de l’adénosine 5’-monophosphate (AMP) Le polymère a été préparé par une approche non-covalente et son efficacité de recapture a été caractérisée par analyse frontale (FA). L’analyse frontale est une technique qui permet de discriminer des interactions spécifiques des non spécifiques et de comprendre les mécanismes de liaison dans des cavités spécifiques. / This thesis report presents the exploration of molecularly imprinted polymers (MIP) for the application in controlled release and targeting antivirus and anticancer drugs. The first part of this study describes the imprinting of vanillin as a monolith. Several strategies were studied: non-covalent, covalent and semi-covalent. The composition of the MIP prepared in each approach was optimized to obtain the best properties and performance. The affinity, selectivity and capacity of MIP were determined. MIPs were evaluated in solid-phase extraction (SPE) of structural analogues in natural samples (vanilla extract, wine). We also present the study of the exploration of spherical beads as potential tools for the controlled release of vanillin. These studies concern the characteristics of uptake and release of the molecule of interest in the aqueous medium on functionalised microspheres supplied by Merck ESTAPOR Microspheres®. The second part of this thesis is devoted to studies on the evaluation of MIP of adenosine 5'-monophosphate (AMP). The polymer was prepared in non-covalent approach and efficiency of binding was characterised using frontal analysis (FA). FA is a useful technique that allows discriminate specific and nonspecific interactions and to understand the binding mechanisms in specific cavities.

Este estudo tem como objetivo central avaliar a influência da secagem por aspersão de nanocápsulas de núcleo lipídico contendo tretinoína nos perfis in vitro de liberação e de penetração cutânea deste fármaco a partir de hidrogéis. Esses experimentos foram conduzidos empregando-se células de difusão de Franz, pele de abdome de porcos (fêmeas), regime de aplicação de doses infinitas e meio receptor composto por tampão fosfato pH 7,4 e etanol (70:30). A secagem por aspersão das suspensões de nanocápsulas, utilizando PVP e lactose (1:1, m/m) a 10% como adjuvantes, forneceu produtos com bons perfis de dispersão em água, bons rendimentos (próximos a 70%), baixos teores de substâncias voláteis, e teores do fármaco acima de 92%. O tipo de produto intermediário, suspensão aquosa ou respectivo pó, utilizado na produção de hidrogéis (G-LNC-TTN e G-LNC-TTN-SD, respectivamente) não influenciou no perfil de liberação in vitro da tretinoína, que se ajustou ao modelo de Higuchi. No estrato córneo houve diferenças nas quantidades de tretinoína penetradas a partir das duas formulações. O G-LNC-TTN levou a uma retenção exponencial do fármaco nessa camada, enquanto para o G-LNC-TTN-SD isso não ocorreu. Essa diferença foi associada à forma de organização das nanocápsulas na matriz do gel. Na epiderme e na derme, ambas as formulações permitiram a chegada de pequenas e constantes quantidades de tretinoína. No compartimento receptor da célula de Franz o fármaco não foi detectado. A pequena permeação da tretinoína para as camadas mais profundas da pele e para o meio receptor são indicativos de baixa absorção sistêmica, e também podem contribuir para a diminuição dos efeitos adversos associados à terapia tópica com essa substância. A secagem das suspensões de nanocápsulas de núcleo lipídico, nas condições utilizadas, forneceu um intermediário em potencial para a produção de formas farmacêuticas semissólidas contendo tretinoína. / This study’s central goal is to assess the influence of spray-drying lipid core nanocapsules on tretinoin in vitro release profiles as well as skin penetration/permeation from hydrogels. These experiments were conducted employing Franz diffusion cells, pig abdominal skin (female), infinite doses regimen and receptor medium composed of phosphate buffer pH 7.4 and ethanol (70:30). Spray-drying of the nanocapsules suspensions, using PVP and lactose (1:1, m/m) at 10% (m/v) as drying adjuvant provided powders with good water dispersion profiles, good yields (around 70%), low volatile substances contents, in addition to drug contents above 92%. Interchanging intermediate products, aqueous suspension or respective powder, used in hydrogel formulation (G-LNC-TTN and G-LNC-TTN-SD, respectively) caused no influence on tretinoin in vitro release profile which was adjusted by Higuchi model. In corneum stratum there were differences in tretinoin quantities which penetrated from those formulations. The G-LNC-TTN provided an exponential retention of the drug on this skin’s layer, although G-LNC-TTN-SD did not. This difference was associated with the nanocapsules organization form in hydrogel matrix. In epidermis and dermis both formulations allowed permeation of constant and low tretinoin quantities. Moreover, at receptor fluid the drug was not detected. The low tretinoin permeation for deeper skin layers and for receptor fluid is low systemic absorption indicative, furthermore, may contribute in reducing adverse effects associated with tretinoin topical therapy. In given conditions, spray-drying of lipid core nanocapsules provided a potential intermediate for production of semi solids pharmaceutical forms containing tretinoin.

Sistemas integrados de produção agrícola e pecuária estão sendo cada vez mais adotados no país e existe um grande potencial, no subtrópico brasileiro, de integrar a pecuária nas grandes extensões de pastagens hibernais cultivadas, antecedendo lavouras de verão, como soja e milho. Nesses sistemas, enquanto o animal é considerado o elemento catalizador e o solo é o compartimento que centraliza e captura as modificações impostas pelo manejo. Neste estudo, investigou-se um sistema com produção de soja-bovinos de corte, em um consórcio de azevém + aveia preta, manejada em diferentes alturas de pastejo (10, 20, 30, 40 cm) e uma área sem pastejo. O experimento foi instalado em maio de 2001, em São Miguel das Missões - RS, em Latossolo Vermelho distroférrico, em sistema plantio direto. Foram abordados aspectos relacionados aos impactos do manejo do sistema sobre os teores e os estoques de carbono e nitrogênio após nove anos da instalação do experimento. Também foi estudada a cinética de liberação de carbono, nitrogênio, fósforo, potássio, cálcio e magnésio, em dois ciclos pastejo-soja (2009/11), a partir da decomposição dos resíduos vegetais, em sacos de decomposição (litter bags). Intensidades de pastejo moderadas a leve (20, 30 e 40 cm de altura do pasto) promoveram aumento nos teores e estoques de carbono orgânico e nitrogênio, total e particulado, semelhantemente ao observado na área sem pastejo. Valores do índice de manejo de carbono (IMC), em comparação com os da área tomada como referência (mata nativa e SP), indicam alta degradação da qualidade da matéria orgânica na maior intensidade de manejo (10 cm). A velocidade da ciclagem dos nutrientes foi maior nas intensidades moderadas de pastejo (20 e 30 cm), tanto dos resíduos da pastagem como do esterco. A decomposição dos resíduos da soja, cultivada na sequência, não foi afetada pelo manejo do pasto. As folhas apresentaram uma decomposição mais rápida, e consequente liberação mais rápida de nutrientes, em relação aos caules. A quantidade de nutrientes liberados dos resíduos em um ciclo pastejo-soja é suficiente em relação à demanda das plantas (pastagem e soja) e, majoritariamente, determinada pelos resíduos do pastejo (pasto + esterco), que foram maiores nas áreas com pastejo leve e nas áreas sem pastejo. / Integrated crop-livestock systems are lately being increasingly used in the country, and there is a great utilization potential in brazilian subtropic region, by integrating catlle production in a large area covered by winter pastures, preceeding summer crops, mostly soybean and corn. The animal, in such systems, is considered the catalizing agent, while the soil is the compartment that captures all the modifications imposed by animal and pasture management This research investigated a soybean-cattle system in a pasture mixture (ryegrass + black oat), managed at different plant heights (10, 20, 30 and 40 cm) and no grazed areas. The experiment was established in May, 2001, in São Miguel das Missões county, Rio Grande do Sul state – Brazil, in a clayey Hapludox, under no-tillage system. The impacts of the integrated system management in total and particulated fractions of carbon and nitrogen were studied nine years after the experiment started. Nutrient (carbon. nitrogen, phosphorus, potassium, calcium and magnesium) cycling was also studied in two soybean-livestock cycles (2009/11), by plant and animal residue decomposition in litter bags. Moderately and light (20 and 30 and 40 cm plant height, respectively) pasture pressure resulted in similar increase of total and particulated carbon and nitrogen stocks and contents, as found in no-grazed area. Carbon managements indexes (CMI), as compared with the reference areas, indicated high degradation of organic matter quality under the most instensive grazing intensity (10 cm of pasture height). Nutrient cycling was higher in moderately grazing (20 and 30 cm pastures height), for pasture and cattle residues. Soybean residue decomposition was not affected by pasture and cattle management; however soybean leaves were more readily decomposed, and in this way, fastly release nutrients, as compared with stem decomposition. The amount of released nutrients in a soybean-cattle cycle is high as compared with plants (pasture and soybean) requirement for high yields and mostly determined by cattle and pasture residues that were higher under light and no grazing intensities, due to higher residue production.

In the context of an increasing production of industrial toxic substances (TIC; Toxic Industrial Compound), the risk of accidental release of hazardous substances is growing in spite of the gradual implementation of safer technological processes and safety improvement measures. To mitigate the consequences of chemical accidents or to prepare preventive protective measures before the accident, it is necessary to know or at least estimate the course of accidents. In particular, it applies to the range of traumatic events and fatal accidents. One of the tools that can express the impact of accidents is modelling programs. This diploma thesis presents a comparison of outputs from two special types of software ? a foreign program the ALOHA and the TerEx developed in the Czech Republic. The purpose of the thesis was to indicate theoretical aspects related to gaseous toxic substances diffusion in the ground atmospheric layer and to describe modelling of their ill effects range. To achieve this objective, scientific literature and consultation with experts were used. The practical section of the thesis aimed at determining to what extent the results of both programs differ when initial conditions were identical. To achieve this goal, the intercomparison of outputs (e.g. hurtful concentration range) of the two programs that provided results for the same input data sets (type and quantity of hazardous substances, environmental temperature, wind speed, degree of cloud cover, weather stability class, type of ground surface) was used. After the assessment of the comparison it is possible to generalize the results stating that the software ALOHA compared to the TerEx is more conservative, which means that the ALOHA software provides longer anticipated ranges of danger. Therefore, it depends on the user (the person responsible ? crisis manager, intervention commander, mayor of the village), which approach they select or recommend ? to prepare a greater or a smaller area for a possible accident (to ensure public awareness, to implement technical measures to mitigate the impact of that accident, to assess the amount of financial resources, etc.). As a subsequent step it would be appropriate to verify the theoretical results experimentally, by field testing, which would be conducted under the same meteorological conditions under which the modelling was made by the mentioned programs. This would thus confirm the legitimacy of the special software use for the purpose of estimating the range of negative effects of chemical accidents.

Orientador: Prof. Dr. Eraldo José Madureira Tavares / Tese (doutorado) - Universidade Federal do ABC, Programa de Pós-Graduação em Biossistemas, 2015. / Atualmente, sistemas de liberação de fármacos usando nanotecnologia tem despertado grande interesse, entretanto, uma área frequentemente ignorada pelos pesquisadores de formulações de liberação controlada é o combate de ectoparasitas em gado. Para superar essa deficiência, foram desenvolvidas neste estudo formulações de nanopartículas visando a aplicações para uso tópico. As nanopartículas foram sintetizadas e caracterizadas através da avaliação da taxa de associação, tamanho, potencial zeta e pH. A cinética de permeação de ivermectina na pele foi simulada em células de Franz. As formulações (doze) apresentaram estabilidade adequada e taxas de associação próximas a 100%. Os ensaios de permeação mostraram que a liberação da ivermectina foi alterada e os perfis de liberação variaram entre as formulações. Duas formulações, nanocápsulas de PLA e de PLGA, ambas obtidas por nanoprecipitação, iniciaram a liberação dentro das 32 h de ensaio de permeação. Essas duas nanocápsulas também apresentaram bons resultados de estabilidade, apresentando tamanho relativamente constante, potenciais zeta normalmente abaixo de -30 mV, índice de polidispersão (IPD) abaixo de 0,2 e diminuição de pH aproximadamente dentro de 1 unidade de pH. A cinética de permeação das duas formulações foi avaliada utilizando-se modelos matemáticos tais como Higuchi, difusão em esferas sólidas e cápsulas, cinética de ordem zero, modelos de dissolução e a equação generalizada de Korsmeyer-Peppas. O perfil de liberação dessas nanocápsulas sugere o possível acúmulo do fármaco no miristato de isopropila, que simula o estrato córneo da pele. As demais formulações requerem estudos adicionais para detectar seus perfis de liberação, e poderiam ser úteis para liberações extremamente longas e depender bastante da erosão dos polímeros. Os resultados obtidos nesta pesquisa são promissores como sistema alternativo para o tratamento de ectoparasitas, visando a aplicações veterinárias. / Drug release systems using nanotechnology are currently among the research programs which have aroused great interest, however, a field being frequently ignored by controlled release formulation researches is the fight against cattle ectoparasites. In order to overcome that deficiency, nanoparticle formulations for topical usage were developed in this research. The nanoparticles were synthetized and characterized with respect to association rate, size, zeta potential and pH. Ivermectin permeation kinetics in skin was simulated in Franz cells. The formulations (12) presented adequate stability and rate of association of about 100%. The release assays have shown that the release of ivermectina was modified and the release profiles varied among the formulations. Two formulations, PLA and PLGA nanocapsules, both prepared by nanoprecipitation, started the release during the 32h of the permeation assay. Both nanocapsules also had good stability results, having relatively constant size, zeta potentials usually below -30 mV, polydispersity index (PDI) below 0.2 and pH decrease within 1 pH unit. The release kinetics of both formulations was assessed using mathematical models such as Higuchi, diffusion in solid spheres and in capsules, zero order, dissolution models, and Korsmeyer-Peppas¿s generalized equation. The release profile of these nanocapsules suggests the possible accumulation of the drug in the isopropyl myristate, which simulates de stratum corneum of the skin. The remaining formulations require additional studies to detect their release profiles, and could be useful for extremely long releases and might depend quite a lot on the polymers erosion. The results of this research are promising as an alternative system for the treatment of ectoparasites, aiming for veterinary usage.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This work aimed the development of polymeric microparticles containing sodium risedronate from Eudragit S100® (MP-EUD) and the blend, Eudragit S100® and Pullulan (MP-EUD-PUL), through spray-drying technique. MP-EUD were obtained with a yield of 54%, encapsulation efficiency of 90%, average particle size of 3.3 μm and presented spherical shape. The moisture content was 8% and the Carr Index and Hausner Factor indicated poor flowability. At pH 1.2 23% risedronate sodium was released after 120 min, while the drug at pH 6.8 took 90 min to reach 99.5%. The mathematical modeling showed that the drug release followed first order kinetics and Fickian diffusion. Tablets prepared by direct compression of MP-EUD using different polyvinylpirrolidone concentrations showed low weight variation, thickness and drug content. Furthermore, they presented low friability and adequate hardness. In vitro studies indicated that no more than 16% of the drug was released in 120 min at pH 1.2. At pH 6.8 the risedronate release was prolonged for 270 min and folowed first order kinetics and Fickian diffusion. Concerning MP-EUD-PUL, three proportions of Eudragit S100® and Pullulan (1:2, 1:1 and 2:1) were studied. Microparticles were obtained with yields ranging from 31% to 42%, encapsulation efficiencies close to 100%, moisture contents lower than 11%, mean particle size in the range of 2.9 μm - 4.8 μm and narrow size distributions. Carr index and Hausner ratio indicated poor flowability. In gastric simulated fluid the microparticles prepared with the highest amount of Eudragit S100® showed the best gastroresistance. In intestinal simulated fluid blend microparticles were able to prolong the drug release. MP-EUD-PUL 2:1 were compressed into tablets with or without a binder. Both tableted microparticles could be obtained with acceptable average weights, drug content close to 100%, sufficient hardness and low friability. In vitro studies showed that tablets maintained the gastroresistance observed for untableted microparticles and were also able to prolong risedronate release. Finally, the formulations developed in this study represent promising alternatives for sodium risedronate oral delivery. / Este trabalho objetivou o desenvolvimento de micropartículas poliméricas contendo risedronato de sódio a partir de Eudragit S100® (MP-EUD) e da blenda, Eudragit S100® e Pullulan (MP-EUD-PUL), através da técnica de secagem por aspersão. As MP-EUD foram obtidas com um rendimento de 54%, eficiência de encapsulamento de 90%, tamanho médio de partícula de 3,3 μm e apresentaram formato esférico. O teor de umidade foi de 8%, o Índice de Carr e o Fator de Hausner indicaram baixa fluidez. Em pH 1,2, 23% do risedronato de sódio foi liberado em 120 min, enquanto que em pH 6,8 o fármaco levou 90 min para ser liberado. A modelagem matemática mostrou que a liberação do fármaco seguiu cinética de primeira ordem e se deu por difusão Fickiana. Comprimidos preparados pela compressão direta das MP-EUD a partir de diferentes concentrações de polivinilpirrolidona apresentaram baixas variações de peso médio, espessura e teor de fármaco. Além disso, apresentaram baixa friabilidade e dureza adequada. Os estudos in vitro mostraram que não mais que 16% do fármaco foi liberado durante 120 min em pH 1,2 enquanto que em pH 6,8 a liberação do fármaco foi prolongada por 270 min, seguindo cinética de primeira ordem e difusão Fickiana. Com relação às MP-EUD-PUL, três proporções de Eudragit S100® e Pullulan (1:2, 1:1 e 2:1) foram estudadas. As micropartículas foram obtidas com rendimento variando entre 31% e 42%, com eficiência de encapsulamento próxima de 100% e umidade abaixo de 11%. O tamanho médio de partícula variou entre 2,9 μm e 4,8 μm com estreita distribuição de tamanho. O Índice de Carr e o Fator de Hausner indicaram baixa fluidez. Em meio gástrico simulado, as micropartículas com maior proporção de Eudragit S100® apresentaram melhor perfil de gastrorresistência, enquanto que em meio intestinal simulado todas foram capazes de prolongar a liberação do fármaco. As MP-EUD-PUL 2:1 sofreram compressão direta na ausência ou na presença de polivilpirrolidona. Os comprimidos microparticulados apresentaram pesos médios aceitáveis, teor de fármaco próximo a 100%, dureza e friabilidade dentro do especificado. Os estudos in vitro mostraram que a gastrorresistência foi mantida e que os comprimidos microparticulados também foram capazes de prolongar a liberação do risedronato. Finalmente, as formulações desenvolvidas neste estudo representam alternativas promissoras para a administração oral do risedronato de sódio.

Made available in DSpace on 2014-06-11T19:32:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-12-13Bitstream added on 2014-06-13T18:42:56Z : No. of bitstreams: 1 vilarinho_ec_dr_jabo.pdf: 465456 bytes, checksum: e0c1e93e1d9ee22febb1950e8418eaab (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Com a adoção de plantas geneticamente modificadas que expressam toxinas de Bacillus thuringiensis há a necessidade de estabelecimento de estratégias para retardar o desenvolvimento da resistência de insetos, tais como áreas de refúgio. Para tanto, informações sobre a dispersão dos insetos alvo desta tecnologia são essenciais para aprimoramento de técnicas de manejo de insetos-praga. Nos estudos de dispersão normalmente são usadas técnicas de marcação-liberação-recaptura. Assim, objetivou-se com este trabalho marcar Diatraea saccharalis e avaliar a capacidade de dispersão de Spodoptera frugiperda. Para a marcação, dois corantes lipossolúveis em diferentes concentrações (100 a 400 ppm), Sudan Red 7B e Solvente Blue, foram adicionados à dieta artificial de D. saccharalis e avaliados sobre parâmetros biológicos do desenvolvimento de lagartas, pupas e adultos (fecundidade e longevidade). A adição dos corantes em dieta artificial fornecida para alimentação de lagartas de D. saccharalis proporcionou a marcação de adultos e ovos em todas as concentrações testadas. No caso da avaliação da capacidade de dispersão de S. frugiperda foram realizados experimentos durante as safras 2005/2006 e 2006/2007. A dispersão se dá por difusão e foi possível registrar distâncias máximas de recaptura de 806 m para machos e 608 m para fêmeas de S. frugiperda. / With the adoption of genetically modified plants expressing Bacillus thuringiensis toxins there is a need of establishing strategies to delay the development of insect resistance (e.g. refugee areas). Thus, information on target insects dispersal are essential to improve pest management techniques. In dispersal studies, markingrelease- recapture techniques are usually used. The objective of this work was to mark Diatraea saccharalis and evaluate the dispersal capacity of Spodoptera frugiperda. For marking D. saccharalis, different concentrations (100 to 400 ppm) of two oil soluble dyes (Sudan Red 7B and Solvent Blue) were added to larval artificial diet. Larval and pupal development as well as adult fecundity and longevity were evaluated. The addition of dyes into the diet marked both adults and eggs, regardless the concentration used. For evaluating the dispersal capacity of S. frugiperda, experiments were carried out during 2005/2006 and 2006/2007 growing seasons. Dispersal is diffused and the maximum recapture distances were 806 m for males and 608 m for females of S. frugiperda.

Original analytical theories are developed for partitioning mixed-mode fractures on rigid interfaces in laminated orthotropic double cantilever beams (DCBs) based on 2D elasticity by using some novel methods. Note that although the DCB represents a simplified case, it provides a deep understanding and predictive capability for real applications and does not restrict the analysis to a simple class of fracture problems. The developed theories are generally applicable to so-called 1D fracture consisting of opening (mode I) and shearing (mode II) action only with no tearing (mode III) action, for example, straight edge cracks, circular blisters in plates and shells, etc. A salient point of the methods is to first derive one loading condition that causes one pure fracture mode. It is conveniently called the first pure mode. Then, all other pure fracture modes can be determined by using this pure mode and the property of orthogonality between pure mode I modes and pure mode II modes. Finally, these 2D-elasticity-based pure modes are used to partition mixed-mode fractures into contributions from the mode I and mode II fracture modes by considering a mixed-mode fracture as the superposition of pure mode I and mode II fractures. The partition is made in terms of the energy release rate (ERR) or the stress intensity factor (SIF). An analytical partition theory is developed first for a DCB composed of two identical linear elastic layers. The first pure mode is obtained by introducing correction factors into the beam-theory-based mechanical conditions. The property of orthogonality is then used to determine all other pure modes in the absence of through-thickness-shear forces. To accommodate through-thickness shear forces, first two pure through-thickness-shear-force pure modes (one pure mode I and one pure mode II) are discovered by extending a Timoshenko beam partition theory. Partition of mixed-mode fractures under pure through-thickness shear forces is then achieved by using these two pure modes in conjunction with two thickness-ratio-dependent correction factors: (1) a shear correction factor, and (2) a pure-mode-II ERR correction factor. Both correction factors closely follow a normal distribution around a symmetric DCB geometry. The property of orthogonality between all pure mode I and all pure mode II fracture modes is then used to complete the mixed-mode fracture partition theory for a DCB with bending moments, axial forces and through-thickness shear forces. Fracture on bimaterial interfaces is an important consideration in the design and application of composite materials and structures. It has, however, proved an extremely challenging problem for many decades to obtain an analytical solution for the complex SIFs and the crack extension size-dependent ERRs, based on 2D elasticity. Such an analytical solution for a brittle interfacial crack between two dissimilar elastic layers is obtained in two stages. In the first stage the bimaterial DCB is under tip bending moments and axial forces and has a mismatch in Young s modulus; however, the Poisson s ratios of the top and bottom layers are the same. The solution is achieved by developing two types of pure fracture modes and two powerful mathematical techniques. The two types of pure fracture modes are a SIF-type and a load-type. The two mathematical techniques are a shifting technique and an orthogonal pure mode technique. In the second stage, the theory is extended to accommodate a Poisson s ratio mismatch. Equivalent material properties are derived for each layer, namely, an equivalent elastic modulus and an equivalent Poisson s ratio, such that both the total ERR and the bimaterial mismatch coefficient are maintained in an alternative equivalent case. Cases for which no analytical solution for the SIFs and ERRs currently exist can therefore be transformed into cases for which the analytical solution does exist. It is now possible to use a completely analytical 2D-elasticity-based theory to calculate the complex SIFs and crack extension size-dependent ERRs. The original partition theories presented have been validated by comparison with numerical simulations. Excellent agreement has been observed. Moreover, one partition theory is further extended to consider the blister test and the adhesion energy of mono- and multi-layered graphene membranes on a silicon oxide substrate. Use of the partition theory presented in this work allows the correct critical mode I and mode II adhesion energy to be obtained and all the experimentally observed behaviour is explained.

Actuellement, la mise au point de systèmes de vectorisation d'agents chimio-thérapeutiques performants fait l'objet d'une intense recherche. Les nanoparticules en particulier sont étudiées, car elles permettent de solubiliser des molécules hydrophobes en milieux aqueux tout en diminuant leur toxicité et leur dégradation. Toutefois, le devenir à long terme des nanoparticules est un paramètre important qu'il faut considérer dans la conception de ces nanovecteurs. Pour cette raison, le développement de nanoparticules auto-assemblées constituées de copolymères à bloc entièrement biocompatibles, biodégradables et aux propriétés de libération contrôlée est recommandé. Dans cette perspective, nous avons étudié les propriétés d'auto-organisation de copolymères greffés amphiphiles de type chitooligosaccharide-grafted-polycaprolactone. Le premier chapitre révèle l'utilisation de l'aniline et de son dérivé alcyne comme un outil efficace pour l'amination réductrice de chitooligosaccharides. Dans le second chapitre, différentes familles de polycaprolactone avec des fonctions azide latérales sont décrites. Le troisième chapitre traite du couplage par chimie « click » de chaque bloc ainsi que de la caractérisation physico-chimique des nanoparticules en solution aqueuse. La réticulation de ses particules a permis d'obtenir les nanogels finaux. Pour conclure, des tests d'encapsulation et de libération contrôlée de la Doxorubicine (avec ou sans ajout de glutathion) ont été effectués / Currently, the development of efficient drug delivery systems has a great attention. Nanoparticles are particularly studied for their capacity to solubilise hydrophobic drugs in aqueous media and to decrease their toxicity and degradability. However, long term compatibility has to be considered in the conception of this nanocarrier. For this reasons, the development of self-assembled particles constituted of biocompatible, biodegradable block copolymers is highly recommended. In this perspective, we have studied the self-assembled properties of chitooligosaccharide-grafted-polycaprolactone copolymers. The first chapter reveals aniline catalysis and its alkyne derivative as an efficient way for reductive amination of chitooligosaccharides. The second chapter describes the synthesis of different polycaprolactones with pendant azide groups. The third chapter is dedicated to the grafting of each bloc performed by “click” chemistry as well as the formation and characterisation of nanoparticle conducted in aqueous media. These nanoparticles were cross-linked to form reduction-sensitive final nanogels. At last, entrapment and controlled Doxorubicine release (with or without glutathione) were explored.

Made available in DSpace on 2016-06-02T19:19:54Z (GMT). No. of bitstreams: 1 DANTAS_Patricia_2011.pdf: 2256820 bytes, checksum: e36b1fbb6b7a53c4ba196910208d1dd3 (MD5) Previous issue date: 2011-12-16 / Financiadora de Estudos e Projetos / Hydrogels derived from cellulose acetate propionate (CAP) and cellulose acetate (CA) were synthesized with the cross-linking agents PMDA (Pyromellitic Dianhydride) and BTDA (Dianhydride 3, 3 ', 4, 4' Benzophenone Tetracarboxylated) with 3:1 stoichiometry in relation to the mass of the crosslinker agent x mass of available hydroxyls in the polymer chain. The gels were obtained in the form of films and particles, the raw materials were characterized with Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), Spectroscopy in Region of Fourier Transform Infrared (FTIR) and in relation to the degree of substitution (GS). The gels synthesized were characterized using FTIR techniques in order to show the esterification, TGA and DSC to perform comparative analysis and study of thermal properties between the CAP and CA reagents and gels, and Scanning Electron Microscopy (SEM) were used for observation of the gels synthesized and the geometry of the particles obtained, the porosity of observation and observation of surface changes, was performed to determine the crosslinking density of the second theory of Flory Rehner, study the density of the gels, and degree of swelling of the study best solvent for swelling of the gels. Gels derived from CAP were tested in the adsorption studies and controlled release of the herbicide paraquat. For the phenomenon of controlled release, we studied the phenomena of transport and release curves. The release profiles were studied by using the mathematical model published by Korsmeyer-Peppas and the mainly results has showed that model was appropriated for process data analysis of controlled release in long periods. / Hidrogéis derivados de Propionato Acetato de Celulose (CAP) e Acetato de Celulose (CA) foram sintetizados com os agentes reticuladores PMDA (Dianidrido Piromelítico) e BTDA (Dianidrido 3, 3´, 4, 4´ Benzofenona Tetracarboxílico), com estequiometrias 3:1 em relação à massa do agente reticulador x massa de hidroxilas disponíveis na cadeia polimérica, com obtenção de géis em formato de filmes e particulados; as matérias-primas foram caracterizadas com Análise Termogravimétrica (TGA), Calorimetria Diferencial de Varredura (DSC), Espectroscopia na Região do Infravermelho com Transformada de Fourier (FTIR) e em relação ao Grau de Substituição (GS). Os géis sintetizados foram caracterizados utilizando as técnicas de FTIR, para evidenciação da esterificação; TGA e DSC para realização de análise comparativa e estudo das propriedades térmicas entre os reagentes CAP e CA e os géis obtidos; e Microscopia Eletrônica de Varredura (MEV), utilizada para observação dos géis sintetizados em relação à geometria das partículas obtidas, observação da porosidade e observação de alterações superficiais; foi realizada a determinação da densidade de ligações cruzadas segundo a Teoria de Flory Rehner; estudo da densidade dos géis, que variaram de 0,4 a 1,51 g/cm3; grau de inchamento que obteve variações entre os diferentes géis de 6,53 à 11,8; e o estudo do melhor solvente para intumescimento dos géis. Nos géis derivados de CAP, foram realizados ensaios de adsorção e liberação controlada do herbicida Paraquat. Para o fenômeno de liberação controlada, foram estudados os fenômenos de transporte e as curvas de liberação; os perfis de liberação foram estudados pelo modelo matemático de Korsmeyer-Peppas; e apresentaram como o gel com maior porcentagem de adsorção e melhor potencial para liberação controlada por longos períodos o gel CAP 3B1.