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Synthèses et assemblages de nanoparticules / Nanoparticles syntheses and assembliesBurel, Céline 25 September 2017 (has links)
Les nanoparticules (NPs) assemblées en architectures 2D ou 3D présentent de nouvelles propriétés optiques, magnétiques et électroniques collectives. Par exemple, des NPs d’argent (Ag) ou d’or (Au) absorbent la lumière à des longueurs d’onde plus grandes lorsqu’elles sont compactées que lorsqu’elles sont éloignées. Tout d'abord, des microparticules de latex et des NPs d’or sont assemblées par la technique de pervaporation microfluidique afin de former des matériaux denses aux dimensions contrôlées. En réduisant la concentration en sels contenus dans les dispersions de particules, ces dernières s’organisent en cristaux hexagonaux. Des matériaux millimétriques constitués de petites particules densément ordonnées sont collectés, offrant ainsi une base solide quant à la conception de nouveaux optomatériaux fonctionnels à l’échelle micrométrique. Ensuite, des NPs d’or et d’argent sont assemblées sur des gouttes d’émulsion afin de fabriquer des matériaux dispersés. En contrôlant les charges et la mouillabilité des particules, celles-ci s’adsorbent et se compactent en surface de gouttes. Les NPs sont ensuite fixées dans une écorce organique par une polymérisation à l’interface de l’émulsion. Dans des conditions bien définies, des microcapsules Au NP-silice et Au NP-polyacrylate respectivement sensibles aux déformations mécaniques et aux variations de pH sont obtenues. Ces microcapsules changent de couleur du fait de l’augmentation de la distance entre les Au NPs lors de la déformation des capsules. Chacune de ces microcapsules étant un capteur à elle toute seule, ces résultats ouvrent la voie vers la conception de nouveaux capteurs à l’échelle micrométrique. / Nanoparticles (NPs) assembled into two- or three-dimensional architectures offer new collective optical, magnetic and electronic properties. For instance, closely packed gold (Au) and silver (Ag) NPs absorb light at higher wavelength than when they are far apart. In the first part of this thesis, the technique of microfluidic pervaporation is used to assemble micron size latex particles and Au NPs in bulky materials of controlled dimensions. By reducing the concentration of salts in the particles dispersions, the particles organize in hexagonal crystals. Millimeter-long materials of small well-organized densely packed particles are collected, offering solid groundwork as for the design of new functional microscale optomaterials. In the second part of this thesis, the assembly of NPs on droplets is used to fabricate dispersed materials. By tuning the charges and wettability of Au and Ag NPs, they adsorb at the surface of emulsion droplets. A subsequent polymerization at the interface of the emulsion allows to lock the NPs inside an organic shell. In well-defined conditions, novel Au NP-silica microcapsules responsive to mechanical strains and Au NP-polyacrylate microcapsules responsive to pH variations are engineered. These microcapsules change color during their deformation due to the increase of the distance between the Au NPs. Each one of the microcapsules being one sensor by itself, these results pave the way as for the design of new microscale sensors.
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Controlled release and targeted drug delivery using polyelectrolyte microcapsulesDeo, Devendra Inder January 2014 (has links)
Polyelectrolyte microcapsules were first established in 1998 as a potential drug delivery vehicle. Despite being well-established, microcapsules have not yet been thoroughly considered as a viable means of targeted drug delivery. This is largely due to the fact that microcapsules are inherently prone to unspecific binding to cells and proteins. Targeted delivery of drugs to specific diseased sites in the body is an area of research that has attracted many studies, particularly in drug deliveries that utilise microparticles. By achieving targeted delivery of a drug, one can increase the efficacy of the treatment, thus, reducing unwanted side effects. This thesis investigates methods which can modify these microcapsules in order to fine tune the release of the encapsulated drug as well as site-specific delivery of these vesicles i.e. obtain spatiotemporal control. To this end, biodegradable microcapsules of varying constituents are manufactured and their biodegradability is indirectly measured through quantification of the release of an encapsulated fluorescent protein (Rhodamine B-BSA). Fluorometry analysis of the supernatants of these microcapsule suspensions indicated that microcapsules synthesised from poly-L-arginine and poly-L-glutamic acid have the ability to encapsulate bovine serum albumin (BSA) with a high encapsulation efficiency (79.7%). Furthermore, they are able to produce a sustained release of BSA over a period of 5 Days. To complement this controlled-release study, an investigation into self-degradable microcapsules was undertaken. To achieve this, proteinase was encapsulated in both biodegradable and non-biodegradable microcapsules of different thickness. Analysis of the protein release over a period of 24 hours revealed that the release profiles of these microcapsules can be successfully controlled. Biodegradable microcapsules released 87% more protein than their non-biodegradable counterpart after 2 hours of incubation in deionised water. This provides conclusive evidence that the biodegradable microcapsules were, indeed, self-degradable. The latter part of this thesis focuses on achieving specific and exclusive targeted delivery using polyelectrolyte microcapsules, with respect to protein substrates. This is accomplished by creating an antibody-functionalised poly(ethylene glycol) (PEG) assembly within the microcapsule structure. Site-specific adsorption of these microcapsules is tested using protein micropatterns. Results obtained from adsorption assays using anti-collagen type IV-functionalised microcapsules show a 600-fold increase in binding to collagen type IV islands, compared to control proteins (fibronectin and BSA). This proves that significant adsorption was achieved on the target protein, with unspecific adsorptions being heavily suppressed on control proteins. Furthermore, similar results were found when microcapsules were functionalised with anti-fibronectin and exposed to fibronectin, highlighting the versatility of this type of biofunctionalisation.
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Microcapsule internalization by cells in vitro caused by physical and biochemical stimuliLiu, Weizhi January 2014 (has links)
There is a growing interest in micro sized vehicles with the function of storing, targeting and controlled releasing of substances during the past few decades. However, delivering the desired drugs inside micro containers to living cells is a particular challenging topic of material science. Microcapsules made of polyelectrolyte multilayers exhibit low- or non-toxicity, appropriate mechanical stability, variable degradation and can incorporate remotely addressable release mechanisms in responding to stimuli and external triggering, making them well suitable for targeted drug delivery to live cells. This study investigates interactions between microcapsules made of synthetic (i.e. PSS/PAH) or natural (i.e. DS/PArg) polyelectrolyte and cells, with particular focus on the effect of the glycocalyx layer on the intake of microcapsules by human umbilical vein endothelial cells (HUVECs). Neuraminidase cleaves N-acetyl neuraminic acid residues of glycoproteins and targets the sialic acid component of the glycocalyx on the cell membrane. Three-dimensional CLSM images reveal that microcapsules functionalized with neuraminidase can be internalized by endothelial cells, whereas ones without neuraminidase are blocked by the glycocalyx layer. Uptake of the microcapsules is most significant in the first 2 hours. Following their internalization by endothelial cells, biodegradable DS/PArg capsules rupture by day 5, however, there is no obvious change in the shape and integrity of PSS/PAH capsules within the period of observation. Results from the study support our hypothesis that the glycocalyx functions as an endothelium barrier to cross membrane movement of microcapsules. Neuraminidase-loaded microcapsules can enter endothelial cells by cleaving the glycocalyx in their close proximity with minimum disruption of the glycocalyx layer, therefore they have high potential to act as drug delivery carriers to pass through the endothelium barrier of blood vessels into the surrounding tissue.
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Reactive MgO and self-healing microcapsules for enhanced well cement performanceMao, Wenting January 2019 (has links)
The annular cement sheath plays a crucial role in ensuring well integrity by providing adequate zonal isolation, stabilizing the formation, and protecting the casing from corrosion. A majority of well integrity problems originate from oil well cement shrinkage and shrinkage-induced cracking, as well as cracking induced by other external stresses. The addition of expansive additives is a commonly used way to compensate for shrinkage. Compared to conventional ettringite-based and CaO-based expansive additives, MgO has many advantages including a thermally stable hydration product, relatively low water requirements for hydration, and designable expansion properties. These make MgO a promising candidate for delivering the desired expansion under the complex and variable underground wellbore environment. Self-healing materials which have the capability for autonomous crack repair are an attractive solution for addressing cracking problems in oil well cement. Engineered additions of healing agents for autonomic self-healing via a delivery system have been reported as effective ways to promote self-healing in cementitious materials. Microcapsules that can be easily added to cement pastes and dispersed through the cement matrix are considered particularly suitable for use in oil well cement. This research project investigates the efficacy of reactive MgO expansive additives to reduce shrinkage, and of sodium silicate microcapsules to improve the self-healing properties of oil well cement, and explores the feasibility of their combined use in a high temperature oil well environment. Three types of reactive MgOs from different reactivity grades, high reactivity N50, medium reactivity MAG-R, and low reactivity 92/200, were characterised in terms of their expansion characteristics in cement paste prisms cured in water, and further tested on their autogenous shrinkage reduction at 80oC. The highly reactive N50 could only partially compensate for autogenous shrinkage, while the less reactive MAG-R and 92/200 completely compensated for autogenous shrinkage. MAG-R and 92/200 also showed effective drying shrinkage reduction at 90% RH. The restrained expansion of MAG-R and 92/200 during an early age was found to significantly improve the cracking resistance of oil well cement. The free expansion of 92/200, with low reactivity, caused significant strength reduction, but under restrained conditions the effect was mitigated as its compressive strength was enhanced by confined expansion. The addition of MAG-R increased compressive strength under both free and restrained conditions. Two groups of sodium silicate microcapsules, T1 with rigid polyurea shells and T2 with rubbery polyurea shells, were characterised in terms of their thermal stability, alkalinity resistance and survivability during cement mixing, and the results verified their suitability for use in oil well cement at the high temperature of 80 oC. The effects of the two types of microcapsules on the self-healing performance of oil well cement at 80 oC were monitored using a variety of techniques. Oil well cement itself showed very little healing capability when cured at 80 oC, but the addition of microcapsules significantly promoted its self-healing performance, showing reduced crack width and crack depth, enhanced tightness recovery against gas permeability and water sorptivity, as well as strength recovery. Microstructure analyses of the cracking surface further verified the successful release of the sodium silicate core and its reaction with the cement matrix to form C-S-H healing products. Both groups of microcapsules showed comparable self-healing efficiency. Their different shell properties mainly influenced the strength of oil well cement, with rigid shell microcapsules causing less strength reduction than rubbery shell microcapsules. The overall performance of oil well cement containing both reactive MgO and microcapsules were evaluated. The combined addition of MgO MAG-R and T1 microcapsules showed similar expansion performance and self-healing efficiency compared to their individual use. The use of MgO MAG-R compensated for the strength reduction caused by the addition of microcapsules, achieving an overall improvement in the cement strength.
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Estudo do desenvolvimento de microcápsulas de polímeros naturais para aplicação em têxteis médicos / Study of the development of microcapsules of natural polymers for application in medical textilesLima, Caroline Santos Alves de 05 September 2017 (has links)
A indústria têxtil busca recuperar a diminuição do ritmo dos negócios, notado principalmente em países desenvolvidos devido ao cenário da economia mundial, por meio da elaboração de têxteis com maior valor agregado. A microencapsulação é uma técnica versátil e flexível que apresenta diversas vantagens, como evitar que o princípio ativo reaja com outros compostos presentes no sistema e possibilitar a liberação controlada, que aumenta potencialmente a eficiência do produto. O principal objetivo deste trabalho foi desenvolver microcápsulas de quitosana e alginato com incorporação de Triclosan, que possui propriedades bactericida e fungicida, para aplicação em substratos têxteis para utilizações médicas. As microcápsulas foram produzidas a partir do método de emulsificação e reticulação, e caracterizadas por Termogravimetria (TG), Calorimetria Exploratória Diferencial (DSC), Espectroscopia no Infravermelho com Transformada de Fourier (FTIR), capacidade de absorção de água e perda de massa, Microscopia Eletrônica de Varredura (MEV), ensaio de atividade bactericida e liberação in vitro. Após caracterizadas, as microcápsulas foram impregnadas em tecidos 100% algodão com ligamentos tela e sarja. Estes foram submetidos a testes físicos e análise de resistência à lavagem. As microcápsulas produzidas apresentaram forma esférica e tiveram 80,78% de eficiência de encapsulação do fármaco. Os ensaios de liberação mostraram que o fármaco não foi liberado em 24h, entretanto, o material apresentou atividade bactericida contra a bactéria gram-positiva S. aureus, com halo de inibição de até 60 mm e também contra a bactéria gram-negativa E. coli, com halo de até 25 mm. Os resultados de resistência à lavagem avaliados por MEV mostraram que as microcápsulas não permenceram no substrato. Entretanto, o material apresentou atividade antibacteriana podendo ser interessante para aplicação em materiais têxteis descartáveis, como bandagens utilizadas na área médica / The textile industry seeks to recover the decrease of the pace of business, noted mainly in developed countries due to the scenario of the world economy, through the development of textiles with higher added value. The microencapsulation is a versatile and flexible technique that presents several advantages such as to avoid that the active ingredient react with other compounds present in the system, and allow controlled release that potentially increases the efficiency of the product. The main objective of this work was to develop microcapsules of chitosan and alginate with incorporation of triclosan, which has bactericidal and fungicide properties, for use in textile substrates for medical uses. The microcapsules were produced from the method of emulsification and crosslinking, and characterized by Thermogravimetry (TG), Differential Scanning Calorimetry (DSC), Infrared Spectroscopy Fourier Transform (FTIR), water absorption capacity and mass loss, Scanning Electron Microscopy (SEM), bactericidal activity assay and in vitro release. After characterized, the microcapsules were impregnated in 100% cotton twill and taffeta woven. Physical tests and analysis of resistance to washing were carried out. The microcapsules produced presented spherical shape and had 80.78% of drug encapsulation efficiency. Release tests showed that the drug was not released in 24 hours, however, the material presented bactericidal activity against the gram-positive bacterium S. aureus, with inhibition halo up to 60 mm and also against the gram-negative bacterium E. coli, with halo of up to 25 mm. The results of washing resistance evaluated by SEM showed that the microcapsules did not remain in the substrate. However, the material showed antibacterial activity and may be interesting for application in disposable textiles, such as bandages used in the medical field
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Microcapsules multicouches à base d'acide hyaluronique comme transporteurs potentiels de médicaments: synthèse, caractérisation et optimisation de propriétésSzarpak, Anna 26 May 2009 (has links) (PDF)
Les microcapsules de polyélectrolytes préparées par dépôt couche-par-couche suscitent depuis plusieurs années un intérêt croissant lié à leurs applications potentielles dans divers domaines, notamment ceux des biotechnologies et de la libération contrôlée de médicaments. L'objectif de ce travail était de développer de nouvelles microcapsules à base d'acide hyaluronique (HA), un polysaccharide biocompatible et biodégradable. La première partie de ce travail a consisté à optimiser les conditions de synthèse de microcapsules à partir de HA et de poly(allylamine) (PAH). Le PAH a par la suite été remplacé par des polymères biocompatibles : la poly(L-lysine (PLL), ou un dérivé quaternisé du chitosane (QCH). L'influence du partenaire polycationique sur la morphologie, ainsi que les propriétés de stabilité, perméabilité et de dégradation enzymatique des capsules a été analysée. L'encapsulation d'un dextrane comme médicament modèle a par ailleurs été démontrée.
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Desenvolvimento de uma bebida funcional a base de caju (Anacardium occidentale L.) com Lactobacillus casei DN 114-001 livre e microencapsuladoSOARES, Bruna Lúcia de Mendonça 23 February 2016 (has links)
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Previous issue date: 2016-02-23 / CNPq / O grande interesse e consumo de alimentos contendo probióticos deve-se aos benefícios trazidos à saúde. Entretanto a maioria desses produtos são de origem láctea, resultando num impedimento para o consumo por alguns grupos populacionais, como intolerantes à lactose, alérgicos à proteína do leite e hipercolesterolêmicos, tornando o uso de alimentos de origem vegetal uma prática promissora. A técnica da microencapsulação contribui para aumentar a sobrevivência dos microrganismos por formar uma barreira física contra condições desfavoráveis. Desta forma, o presente estudo tem como objetivo desenvolver uma bebida funcional à base de caju adicionada de Lactobacillus casei, livre ou microencapsulado com matriz alginato de cálcio-quitosana. Microcápsulas foram preparadas pelo método de emulsão/gelificação interna, com o alginato como agente encapsulante e posterior revestimento das esferas com quitosana. As microcápsulas de L. casei foram caracterizadas quanto à morfologia, tamanho das partículas e rendimento de encapsulação. A bebida de caju foi elaborada com 45% de polpa e adição de 10% de açúcar e teve sua composição físico-química e nutricional detalhada. As bebidas controle (sem probióticos), com L. casei livres e com microcápsulas foram armazenadas em refrigeração (4°C) por 4 semanas, análises físico-químicas e microbiológicas foram realizadas nos tempos 0, 7, 14, 21 e 28 dias. Simulações gastrointestinais (SGI) in vitro, no início e final do armazenamento, foram realizadas para avaliar a taxa de sobrevivência das células. Foram realizados testes de aceitabilidade e intenção de compra com o objetivo de obter informações sobre a aceitação do consumidor quanto as três formulações da bebida de caju. Durante SGI, L. casei livre perdeu toda viabilidade, enquanto que células encapsuladas mostraram resistência, reduzindo 1,42 log UFC após simulação gástrica e <1 log UFC ao termino da simulação intestinal. Após 28 dias de estocagem, bebidas contendo microcápsulas e células livres apresentaram 10,2 e 8,1 log UFC/mL, respectivamente. As características físico-químicas mantiveram-se estáveis durante armazenamento e frente bebida controle (sem probióticos). A análise sensorial demonstrou que as bebidas foram aceitas pelos provadores, apesar das microesferas terem sido percebidas. Concluímos que bebida de caju é um substrato favorável para sobrevivência de L. casei livre e microencapsulado por 28 dias e que a microencapsulação é uma técnica promissora para prolongar a viabilidade das células e a sobrevivência em SGI. / The great interest and consumption of probiotic foods is due to the health benefits, however most of these products are of dairy origin, resulting in an impediment to consumption for some population groups, as lactose intolerant, allergic to milk protein and hypercholesterolemic, which makes the use of foods of vegetable origin, for the development of functional products, a promising practice. The microencapsulation technique increases the survival of microorganisms in hostile environments, as the gastric juice, assisting the arrival of a greater number of viable bacteria to the intestine. Thus, this study aims to develop a functional beverage cashew apple added of Lactobacillus casei, free or microencapsulated with matrix calcium alginate-chitosan. The microcapsules are prepared by the emulsification/ internal gelation method, with calcium alginate as encapsulating agents and subsequent coating of the beads with chitosan. The microcapsules produced are characterized for morphology, particle size and encapsulation efficiency. The cashew apple beverage was prepared with 45% pulp and adding 10% sugar and had its physical-chemical and nutritional composition detailed. Beverages control (no probiotics), with L. casei free and with microcapsules were stored in refrigerator (4°C) for 4 weeks, physico-chemical and microbiological analyzes were performed on days 0, 7, 14, 21 and 28 days. Gastrointestinal simulations (SGI), in vitro, at the beginning and end of storage, were performed to evaluate the survival rate of the cells. Acceptability and purchase intent tests were performed in order to obtain information about consumer acceptance as the three formulations of cashew apple beverages. During SGI, L. casei free lost all viability, while encapsulated cells showed resistance, reducing 1.42 log CFU after gastric simulation and <1 CFU log at the end of the intestinal simulation. After 28 days of storage, beverage containing microcapsules and free cells showed 10.2 and 8.1 log CFU / mL, respectively. The physico-chemical characteristics were stable during storage and front control beverage (no probiotics). Sensory analysis showed that the drinks were accepted by the judges, despite the microspheres have been perceived. Conclude that cashew apple beverage is a favorable substrate for L. casei free and microencapsulated survival for 28 days and that microencapsulation is a promising technique to prolong cell viability and survival in SGI.
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Estudo do desenvolvimento de microcápsulas de polímeros naturais para aplicação em têxteis médicos / Study of the development of microcapsules of natural polymers for application in medical textilesCaroline Santos Alves de Lima 05 September 2017 (has links)
A indústria têxtil busca recuperar a diminuição do ritmo dos negócios, notado principalmente em países desenvolvidos devido ao cenário da economia mundial, por meio da elaboração de têxteis com maior valor agregado. A microencapsulação é uma técnica versátil e flexível que apresenta diversas vantagens, como evitar que o princípio ativo reaja com outros compostos presentes no sistema e possibilitar a liberação controlada, que aumenta potencialmente a eficiência do produto. O principal objetivo deste trabalho foi desenvolver microcápsulas de quitosana e alginato com incorporação de Triclosan, que possui propriedades bactericida e fungicida, para aplicação em substratos têxteis para utilizações médicas. As microcápsulas foram produzidas a partir do método de emulsificação e reticulação, e caracterizadas por Termogravimetria (TG), Calorimetria Exploratória Diferencial (DSC), Espectroscopia no Infravermelho com Transformada de Fourier (FTIR), capacidade de absorção de água e perda de massa, Microscopia Eletrônica de Varredura (MEV), ensaio de atividade bactericida e liberação in vitro. Após caracterizadas, as microcápsulas foram impregnadas em tecidos 100% algodão com ligamentos tela e sarja. Estes foram submetidos a testes físicos e análise de resistência à lavagem. As microcápsulas produzidas apresentaram forma esférica e tiveram 80,78% de eficiência de encapsulação do fármaco. Os ensaios de liberação mostraram que o fármaco não foi liberado em 24h, entretanto, o material apresentou atividade bactericida contra a bactéria gram-positiva S. aureus, com halo de inibição de até 60 mm e também contra a bactéria gram-negativa E. coli, com halo de até 25 mm. Os resultados de resistência à lavagem avaliados por MEV mostraram que as microcápsulas não permenceram no substrato. Entretanto, o material apresentou atividade antibacteriana podendo ser interessante para aplicação em materiais têxteis descartáveis, como bandagens utilizadas na área médica / The textile industry seeks to recover the decrease of the pace of business, noted mainly in developed countries due to the scenario of the world economy, through the development of textiles with higher added value. The microencapsulation is a versatile and flexible technique that presents several advantages such as to avoid that the active ingredient react with other compounds present in the system, and allow controlled release that potentially increases the efficiency of the product. The main objective of this work was to develop microcapsules of chitosan and alginate with incorporation of triclosan, which has bactericidal and fungicide properties, for use in textile substrates for medical uses. The microcapsules were produced from the method of emulsification and crosslinking, and characterized by Thermogravimetry (TG), Differential Scanning Calorimetry (DSC), Infrared Spectroscopy Fourier Transform (FTIR), water absorption capacity and mass loss, Scanning Electron Microscopy (SEM), bactericidal activity assay and in vitro release. After characterized, the microcapsules were impregnated in 100% cotton twill and taffeta woven. Physical tests and analysis of resistance to washing were carried out. The microcapsules produced presented spherical shape and had 80.78% of drug encapsulation efficiency. Release tests showed that the drug was not released in 24 hours, however, the material presented bactericidal activity against the gram-positive bacterium S. aureus, with inhibition halo up to 60 mm and also against the gram-negative bacterium E. coli, with halo of up to 25 mm. The results of washing resistance evaluated by SEM showed that the microcapsules did not remain in the substrate. However, the material showed antibacterial activity and may be interesting for application in disposable textiles, such as bandages used in the medical field
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Clay-Coated Polyurea Microcapsules for Controlled ReleaseHickey, Janice N. 03 1900 (has links)
<p> Polyurea microcapsules are micron-scale, hollow polymer spheres commonly used in agriculture to encapsulate pesticides for controlled diffusive release onto target crops. Diffusion of these active materials through a protective polymer wall offers a safer and more effective method of delivery compared to the direct spraying of crops with toxicants. The approach we are taking to control the release rate is to coat pre-formed porous polyurea capsules with a separate release-controlling outer layer. This allows us to separately optimize the load-bearing capsule wall and the release control layer, an approach commonly used in other membrane diffusion systems.</p> <p> Montmorillonite clay incorporation into polymer matrices can reduce membrane permeability by forcing diffusants to take a tortuous path around the stacked silicate sheets. Effective formation of clay-polyurea composites requires the delamination of clay particles into thin sheets with high aspect ratios, and their incorporation into polyurea microcapsules either during interfacial polymerization, or post-polymerization. The net negative surface charge of the silicate sheets should facilitate their initial binding to the cationic polyurea surfaces, as well as subsequent binding of polycations to the clay-coated polyurea capsules to create layer-by-layer (LbL) capsule assemblies with
decreasing release rates of internal materials.</p> <p> The main focus of this project is to gain a fundamental understanding of montmorillonite clay and polyurea microcapsules, and the development of a model polyurea composite capsule for release rate analysis. Emphasis will be placed on the reduced permeability of microcapsules coated with clay by LbL assembly post-polymerization, followed by an exploration of further layering with polycations.</p> / Thesis / Master of Science (MSc)
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Polymeric Nanoparticles and Microcapsules for Biomedical ApplicationsSingh, Andrew January 2024 (has links)
Nanoparticle-based delivery vehicles have received substantial interest in the field of drug delivery particularly pertaining to chemotherapeutics. By virtue of their size, nanoscale drug delivery vehicles overcome many obstacles encountered by traditional systems. Moreover, nanocarriers can be fabricated to be ‘smart’, meaning they can be responsive to internal stimuli relating to the microenvironment of the tumor and/or external stimuli that can be delivered non-invasively from outside of the body. One such external trigger is ultrasound, well-known for its role in biomedical imaging based on its wide availability, non-invasiveness, and safety but increasingly being applied for drug delivery.
This thesis proposes solutions to two key challenges associated with locally-targeted polymer-based drug delivery: enhanced tumor accumulation and externally-triggered control over release kinetics. In the former case, brush polymer PLA-PEG analogues are synthesized and explored to correlate how the architecture of these brush blocks affects the resulting self-assembled nanoparticle size, zeta potential, cytotoxicity in vitro, circulation time, and accumulation profiles in vivo. Indeed, brush copolymer analogues allow for copolymerization with additional monomers while conserving ‘stealth properties of linear copolymers, as well as exhibit superior circulation times and longer-term tumor accumulation. In the latter case, a new ultrasound-triggered drug delivery platform is designed consisting of a hollow polymeric shell in which silica “corks” are entrapped; the application of ultrasound can exploit the high difference in the compressibility between the polymeric shell and the silica corks to pop out or otherwise perturb the cork particles, allowing for both on-demand drug release as well as a pulsatile release profiles to be achieved. Overall, by manipulating the surface properties and/or morphologies of polymer-based micro/nanoparticles, the results of this thesis show that key challenges in local drug delivery can be addressed and applied specifically to applications in cancer therapy. / Dissertation / Doctor of Philosophy (PhD) / Drug delivery vehicles attempt to address many of the shortcomings of traditional therapeutics, in particular their low solubility and a lack of tissue targeting, which result in poor efficacy and unwanted side-effects. Polymers specifically have been commonly employed in biomedical applications as there are a wide range of biodegradable polymers that do not cause adverse effects during intended application and can be removed from the body through normal biological function. More recently, more advanced, ‘smart’ materials have been developed that can respond to internal or external stimuli to better address treatment needs. This thesis presents novel polymer-based drug delivery vehicles with new structures useful to passively target particular sites in the body and/or alter drug release profiles, enabling improved drug efficacy and reduced side-effects.
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