Spelling suggestions: "subject:"nanoemulsions"" "subject:"nanoémulsions""
1 |
Hierarchically Porous Silica Materials for the Encapsulation of Molecules of Interest / Matériaux silicatés à porosité hiérarchisée pour l'encapsulation de molécules d'intérêtsRiachy, Philippe 14 March 2016 (has links)
Ce travail porte sur la préparation de matériaux silicatés à porosité hiérarchisée pour l'encapsulation de molécules d'intérêt dans le domaine de la pharmacie et en tant que biocatalyseur. Afin d’atteindre cet objectif, les nano-émulsions sont choisies comme empreinte pour créer les macropores du matériau en raison de la taille homogène et réduite des gouttelettes de l’émulsion (inférieure à 100 nm). Pour cela le système Remcopal 4/décane/eau est investi en déterminant les conditions les plus optimales de formation de nano-émulsion, via les méthodes d'inversion de phases. L’ajout de micelles aux nano-émulsions ne déstabilise pas les émulsions et permet la formation d’un réseau de mésopores organisés selon une symétrie hexagonale. Les matériaux hybrides issus des matériaux poreux contenant encore la phase organique sont dopés par le ketoprofène en vue d’étudier la libération de ce dernier. Celle-ci se révèle sensible au pH. De plus, cette étude de la libération du kétoprofène à partir du matériau méso-macroporeux indique qu'elle est assistée par les micelles qui sont solubilisées dans la solution réceptrice. Le deuxième objectif de ce travail est d'utiliser ces matériaux poreux en tant que biocatalyseur pour la synthèse de biodiesel à partir d'huile de colza. Pour cette application, il est nécessaire que les matériaux résistent à l’immersion dans des milieux aqueux. L’étude de la stabilité hydrothermale a montré que le matériau calciné présente la meilleure stabilité dans l’eau bouillante. Par ailleurs, le matériau peut résister jusqu’à 550°C, la structure ne subissant que des dégradations mineures. Nous avons également utilisé un matériau silicaté à double mésoporosité préparé à partir de micelles fluorées et hydrogénées coexistant dans une même solution. L'évaluation thermique et hydrothermale indique que ces matériaux présentent deux cinétiques de déstructuration qui correspondent à chacune des deux matrices ayant deux tailles de pores différents. L’immobilisation de la lipase Mml est étudiée sur le matériau méso-macroporeux calciné et sur le matériau à double mésoporosité. Les isothermes d'adsorption ont permis de mettre en évidence que le matériau à double mésoporosité peut encapsuler plus d’enzymes que son homologue méso-macroporeux. L’activité enzymatique, au regard des réactions de transestérification, est de façon inverse plus importante avec le matériau méso-macroporeux calciné / This work concerns the preparation of silica materials with hierarchical porosity for the encapsulation of molecules of interest in the field of drug delivery and as biocatalysts. In order to reach this goal, the nano-emulsions were chosen as templates for the macropores of the material because of the homogeneous and small size of the emulsion droplets (less than 100 nm). The system Remcopal 4/decane/water was investigated and the optimal conditions for which nano-emulsion is formed via the phase inversion methods were determined. Adding micelles to the nano-emulsions does not affect its stability and can form a network of mesopores organized with a hexagonal symmetry. Hybrid materials which are hierarchically porous materials where the organic phase is still present, were doped with ketoprofen to study its release, which proved to be pH sensitive. Moreover, the study of the release of ketoprofen from the meso-macroporous material indicates that it is assisted by the micelles which are solubilized in the release medium. The second objective of this work was to use these porous materials as a biocatalyst for biodiesel synthesis from colza oil. For this application it was necessary that the materials are resistant to immersion in aqueous media. The study of the hydrothermal stability shows that the calcined material has the best stability in boiling water. Moreover, the material can withstand up to 550 ° C, the structure undergoes only minor damages. We also used a dual-mesoporous silica material prepared from hydrogenated and fluorinated micelles coexisting in the same solution. Thermal and hydrothermal evaluation indicates that these materials have two different decay kinetics corresponding to each of the two matrices having different pore sizes. The immobilization of lipase Mml was studied on the meso-macroporous calcined material and the dual-mesoporous material. The adsorption isotherms were used to demonstrate that the dual-mesoporous material can encapsulate more enzymes than its meso-macroporous counterpart. On the other hand, the enzyme activity, evaluated by the transesterification reactions, is more important for the calcined meso-macroporous material
|
2 |
Novel 3D in vitro models based on multicellular tumor spheroids to test anticancer drugs and drug delivery vehicles / Nouveaux modèles 3D in vitro à base de sphéroïdes multicellulaires tumoraux pour tester des substances anticancéreuses et des vecteurs de délivrance de médicamentsAkasov, Roman 07 March 2017 (has links)
Les sphéroïdes multicellulaires tumoraux (SMT) constituent un outil prometteur dans le domaine de l’étude biologique des tumeurs. Le but de la thèse était de développer une technique de la formation de SMT et de démontrer la disponibilité de ces sphéroïdes comme modèle in vitro 3D pour tester l’efficacité de principes actifs anticancéreux ainsi que celle de formulations de délivrance de médicaments. L'effet d’auto-assemblage de cellules induit par une addition des peptides RGD cycliques a été étudié pour 16 lignées cellulaires de différentes origines. Le peptide cyclique RGDfK et sa modification avec le cation triphenylphosphonium (TPP) ont permis de mettre en évidence l’induction de formation de sphéroïdes. Les sphéroïdes ont été employés comme modèles pour évaluer la cytotoxicité de principes actifs antitumoraux (doxorubicine, curcumine, temozolomide) et un certain nombre de formulations nano- et micrométriques (microréservoirs, nano-émulsions et micelles). / Multicellular tumor spheroids (MTS) are a promising tool in tumor biology. The aim of the Thesis was to develop a novel highly reproducible technique for MTS formation, and to demonstrate the availability of these spheroids as 3D in vitro model to test anticancer drugs and drug delivery vehicles. Cell self-assembly effect induced by an addition of cyclic RGD-peptides directly to monolayer cultures was studied for 16 cell lines of various origin. Cyclo-RGDfK peptide and its modification with triphenylphosphonium cation (TPP) were found to induce spheroid formation. The spheroids were used as a model to evaluate the cytotoxicity of antitumor drugs (doxorubicin, curcumin, temozolomide) and a number of nano- and micro- formulations (microcontainers, nano-emulsions and micelles).
|
3 |
Formulation de nano-particules iodées comme agents de contraste a longue rémanence vasculaire pour tomodensitométrie / Formulation of iodinated nano-particles as micro-CT blood pool contrast mediaHallouard, François 12 December 2012 (has links)
L’objectif de cette thèse est de réaliser un agent de contraste vasculaire pour tomodensitométrie utilisable en préclinique. En collaboration avec le laboratoire de biogalénique de Strasbourg, ce travail a permis d’obtenir des nano-émulsions iodées produites par diffusion spontanée de surfactif et des nanoparticules iodées produites par ”émulsion - diffusion de solvant”, comme agent de contraste vasculaire. Ces émulsions et particules polymériques présentent en effet, un temps de rémanence vasculaire de plusieurs heures, un pouvoir contrastant suffisant pour un usage en tomodensitométrie (compris entre 170 et 400 HU), la possibilité de les administrer par intraveineuse et une stabilité de plusieurs mois. Les nano-émulsions, notamment celles produites à partir de Lipiodol®, sont les plus prometteuses comme agents de contraste vasculaire de par leur forte radiopacité (475 ± 30 HU) et leur rémanence vasculaire (T1/2 of 4.1 ± 1.10 h). Les nanoparticules iodées à base de PCL présentent un pouvoir contrastant inférieur (168 ± 13 HU) mais elles sont connus pour leur capacité à modifier la libération du principe actif encapsulé. De ce fait même si les agents de contraste de nature lipidique ou ceux inorganiques sont plus performant, elles restent intéressantes pour une visualisation rapide de la distribution du principe actif dans l’organisme. Cette thèse par ailleurs, apporte plusieurs éléments pour la compréhension de la formulation des nano-émulsions obtenues par diffusion spontanée de surfactif et celle des nanoparticules produites par ”émulsion - diffusion de solvant”. Concernant les nano-émulsions, l’influence de l’iodation des huiles et du surfactif a été étudiée autant sur le plan pharmacotechnique que ceux toxicologique et pharmacocinétique. Concernant les nanoparticules à base de PCL, nous avons montré que l’impact du type d’huile et de l’iodation, des polymères PCL et PCL-mPEG et de diverses méthodes de concentration sur la formulation / The aim of this thesis is to formulate a blood pool contrast agent for preclinical X-ray imaging application. In collaboration with the galenic laboratory of Strasbourg, this work has allowed to obtain iodinated nano-emulsions produced by spontaneous diffusion of surfactant and nano-particles produced by iodine ”emulsion - solvent diffusion” as blood pool contrast agent. These emulsions and polymer particles present indeed a vascular persistence of several hours, a sufficient contrast to be use in computed tomography (between 170 and 400 HU), the ability to be administered intravenous and stability of several months. Nano-emulsions, including those produced from Lipiodol®, are the most promising as blood pool contrast media by their high radiopacity (475 ± 30 HU) and vascular persistence (T1/2 of 4.1 ± 1.10 h). Iodinated nano-particles of PCL have a lower X-ray attenuation (168 ± 13 HU), but they are known for their control release of the encapsulated substances. Therefore even if inorganic or lipidic contrast agents show a better contrast, they remain attractive for rapid visualization of the co-encapsulated substance distribution in the body. This thesis also introduced several features for understanding the formulation of nano-emulsions obtained by spontaneous diffusion of surfactant and the nano-particles produced by ”emulsion - solvent diffusion.”
|
4 |
Desenvolvimento e avaliação do processo de obtenção de emulsões múltiplas A/O/A em etapa única empregando óleo de canola e tensoativo não iônico derivado do óleo de rícino / Development and evaluation of the production process of multiple emulsions W/O/W by one step employing canola oil and derivative castor oil non ionic surfactantMorais, Jacqueline Moreira de 04 June 2008 (has links)
As emulsões múltiplas mostram-se como veículos promissores em várias áreas das ciências cosmética e farmacêutica. O estudo do método de obtenção de emulsões múltiplas em etapa única é ferramenta útil para elucidação de seus aspectos físico-químicos e para viabilizar sua aplicação tecnológica. O objetivo da pesquisa foi desenvolver e caracterizar os aspectos físico-químicos do processo de emulsificação em etapa única, das emulsões múltiplas A/O/A obtidas e dos tensoativos empregados. Testes preliminares de estabilidade e avaliação do seu perfil de liberação (cafeína) foram realizados. Nanoemulsões foram inicialmente obtidas pela metodologia proposta, resultado de processo de emulsificação por inversão de fases. Suas características físico-químicas foram determinadas (valores de pH, potencial zeta e granulometria) e a influência de aditivos avaliada. Para o desenvolvimento da emulsão múltipla foram realizadas análises qualitativas e quantitativas das variáveis relevantes à composição (tipo de fase oleosa, de tensoativo hidrofílico, valor de EHL, emprego de diagrama ternário) e ao método de emulsificação (temperatura de aquecimento das fases e de emulsificação, ordem de adição e velocidade de agitação). Os estudos das propriedades físico-químicas dos tensoativos e do filme interfacial formado (cloud point, tensão superficial, CMC, reologia interfacial, reologia de fluxo e isotermas de Langmuir) foram primordiais para compreensão dos fenômenos envolvidos e relevantes ao processo de emulsificação proposto. As emulsões múltiplas foram caracterizadas quanto aos aspectos macro e microscópico, granulometria, valores de pH, potencial zeta, viscosidade relativa, perfil reológico e influência da adição de macromoléculas. A temperatura de manipulação e de emulsificação (78±2grausC) foram parâmetros fundamentais para obtenção destes sistemas em etapa única. Seus aspectos macro e microscópico foram extremamente dependentes da temperatura de emulsificação. Os resultados indicam glóbulos múltiplos consideravelmente menores do que os relatados pela literatura. Foi possível observar, no intervalo de temperatura considerado crítico para o processo, valores de tensão superficial/interfacial mínimos. Os resultados de elasticidade superficial sugerem que o comportamento das moléculas de tensoativos, em associação ou não, foi marcadamente influenciado pela temperatura e que o aumento do número de moléculas do tensoativo hidrofólico na superfície foi desfavorável as interações intramoleculares. A isoterma para os tensoativos em associação e em função da temperatura exibiu marcante inflexão para a faixa de temperatura crítica. Este comportamento indica uma dramática alteração na microestrutura do filme interfacial. O processo de encapsulação foi considerado eficiente. Os resultados obtidos indicam que, no atual estágio de desenvolvimento, não foi possível definir um perfil de liberação para a emulsão múltipla em análise. O método de emulsificação escolhido permitiu a obtenção de sistema múltiplo em etapa única, determinado pelas características físico-químicas dos tensoativos empregados, em especial do tensoativo hidrofílico derivado do óleo de rícino e do processo proposto. A formação de emulsões múltiplas anormais não ocasionais ou momentâneas sugere uma combinação dos processos de inversão de fases transicional, influência do emprego de tensoativos não-iônicos etoxilados, e catastrófica, influência da razão entre o volume da fase dispersa e dispersante. As emulsões múltiplas obtidas apresentaram difícil reprodutibilidade microestrutural; entretanto podem ser consideradas estáveis frente às metodologias de avaliação e análise empregadas. / Multiple emulsions are potential vehicles not only for the cosmetic science, but also for the pharmaceutical science. Study the manufacture process of multiple emulsions by one step is a useful tool for understanding their physical-chemistry aspects and making their technological application practicable as well. The goals of this research were to development and characterize the physical chemistry features of the emulsification process by one step, the W/O/W multiple emulsions produced and the surfactants employed. Preliminary stability tests and evaluation of the release profile (caffeine) were carried out. Initially, nano-emulsions were produced by the proposed methodology, resulting from phase inversion emulsification process. Their physical chemistry aspects (pH and zeta potential values and size distribution) and electrolytes addition influence were evaluated. In order to develop the multiple emulsions, noteworthy qualitative and quantitative variables related to the composition (oil phase and hydrophilic surfactant types, HLB values, phase diagram) and to emulsification process (heating and emulsification temperatures, addition order and agitation speed) were analyzed. Analyses of the physical chemistry aspects of the surfactants in solution and their interfacial film (cloud point, surface tension, CMC, interfacial and flux rheology, and Langmuir isotherms) were essential in order to understand the phenomena related to proposed emulsification process. Multiple emulsion analyses (macroscopic, microscopic, size distribution, pH and zeta potential values, relative viscosity, rheological profile and macromolecule addition influence) were carried out. Production and emulsification temperatures (78±2grausC) were fundamental parameters in order to obtain multiple droplets by one step. Their macro and microscopic aspects were completely conditioned by the emulsification temperature. The sizes of the multiple droplets obtained were significantly smaller than those reported in the literature. For the critical temperature range, the minimum surface tension values were reached. Surface elasticity results suggest that the behavior of the surfactant molecules, in association or not, was fundamentally influenced by the temperature. Increasing surfactant molecule moieties on the surface, the intra molecular interactions were misplaced. The Langmuir isotherm as a function of the temperature demonstrated distinctive behavior for the critical temperature range, where the transition phase into solid state and soon afterwards some collapse could be observed. This phenomenon indicated some dramatic alteration of the surface film microstructure. The encapsulation process was regarded as efficient. The release profile studies demonstrated that the dispersed system in analysis was not ready yet for this research stage. The proposed emulsification process was able to produce multiple droplets by one step; moreover this result presented direct influence of the surfactant physical chemistry features, particularly the hydrophilic one, castor oil derivate, and of the methodology employed. The abnormal, non-occasional and non-transitory, multiple emulsion formation suggest a combination of transitional (ethoxylated non ionic surfactant influence), and catastrophic (dispersed/dispersant ratio influence) phase inversion processes. The obtained multiple emulsions presents microstructure aspects were not easily reproducible; however those were regarded stable for the analysis methodology employed.
|
5 |
Desenvolvimento e avaliação do processo de obtenção de emulsões múltiplas A/O/A em etapa única empregando óleo de canola e tensoativo não iônico derivado do óleo de rícino / Development and evaluation of the production process of multiple emulsions W/O/W by one step employing canola oil and derivative castor oil non ionic surfactantJacqueline Moreira de Morais 04 June 2008 (has links)
As emulsões múltiplas mostram-se como veículos promissores em várias áreas das ciências cosmética e farmacêutica. O estudo do método de obtenção de emulsões múltiplas em etapa única é ferramenta útil para elucidação de seus aspectos físico-químicos e para viabilizar sua aplicação tecnológica. O objetivo da pesquisa foi desenvolver e caracterizar os aspectos físico-químicos do processo de emulsificação em etapa única, das emulsões múltiplas A/O/A obtidas e dos tensoativos empregados. Testes preliminares de estabilidade e avaliação do seu perfil de liberação (cafeína) foram realizados. Nanoemulsões foram inicialmente obtidas pela metodologia proposta, resultado de processo de emulsificação por inversão de fases. Suas características físico-químicas foram determinadas (valores de pH, potencial zeta e granulometria) e a influência de aditivos avaliada. Para o desenvolvimento da emulsão múltipla foram realizadas análises qualitativas e quantitativas das variáveis relevantes à composição (tipo de fase oleosa, de tensoativo hidrofílico, valor de EHL, emprego de diagrama ternário) e ao método de emulsificação (temperatura de aquecimento das fases e de emulsificação, ordem de adição e velocidade de agitação). Os estudos das propriedades físico-químicas dos tensoativos e do filme interfacial formado (cloud point, tensão superficial, CMC, reologia interfacial, reologia de fluxo e isotermas de Langmuir) foram primordiais para compreensão dos fenômenos envolvidos e relevantes ao processo de emulsificação proposto. As emulsões múltiplas foram caracterizadas quanto aos aspectos macro e microscópico, granulometria, valores de pH, potencial zeta, viscosidade relativa, perfil reológico e influência da adição de macromoléculas. A temperatura de manipulação e de emulsificação (78±2grausC) foram parâmetros fundamentais para obtenção destes sistemas em etapa única. Seus aspectos macro e microscópico foram extremamente dependentes da temperatura de emulsificação. Os resultados indicam glóbulos múltiplos consideravelmente menores do que os relatados pela literatura. Foi possível observar, no intervalo de temperatura considerado crítico para o processo, valores de tensão superficial/interfacial mínimos. Os resultados de elasticidade superficial sugerem que o comportamento das moléculas de tensoativos, em associação ou não, foi marcadamente influenciado pela temperatura e que o aumento do número de moléculas do tensoativo hidrofólico na superfície foi desfavorável as interações intramoleculares. A isoterma para os tensoativos em associação e em função da temperatura exibiu marcante inflexão para a faixa de temperatura crítica. Este comportamento indica uma dramática alteração na microestrutura do filme interfacial. O processo de encapsulação foi considerado eficiente. Os resultados obtidos indicam que, no atual estágio de desenvolvimento, não foi possível definir um perfil de liberação para a emulsão múltipla em análise. O método de emulsificação escolhido permitiu a obtenção de sistema múltiplo em etapa única, determinado pelas características físico-químicas dos tensoativos empregados, em especial do tensoativo hidrofílico derivado do óleo de rícino e do processo proposto. A formação de emulsões múltiplas anormais não ocasionais ou momentâneas sugere uma combinação dos processos de inversão de fases transicional, influência do emprego de tensoativos não-iônicos etoxilados, e catastrófica, influência da razão entre o volume da fase dispersa e dispersante. As emulsões múltiplas obtidas apresentaram difícil reprodutibilidade microestrutural; entretanto podem ser consideradas estáveis frente às metodologias de avaliação e análise empregadas. / Multiple emulsions are potential vehicles not only for the cosmetic science, but also for the pharmaceutical science. Study the manufacture process of multiple emulsions by one step is a useful tool for understanding their physical-chemistry aspects and making their technological application practicable as well. The goals of this research were to development and characterize the physical chemistry features of the emulsification process by one step, the W/O/W multiple emulsions produced and the surfactants employed. Preliminary stability tests and evaluation of the release profile (caffeine) were carried out. Initially, nano-emulsions were produced by the proposed methodology, resulting from phase inversion emulsification process. Their physical chemistry aspects (pH and zeta potential values and size distribution) and electrolytes addition influence were evaluated. In order to develop the multiple emulsions, noteworthy qualitative and quantitative variables related to the composition (oil phase and hydrophilic surfactant types, HLB values, phase diagram) and to emulsification process (heating and emulsification temperatures, addition order and agitation speed) were analyzed. Analyses of the physical chemistry aspects of the surfactants in solution and their interfacial film (cloud point, surface tension, CMC, interfacial and flux rheology, and Langmuir isotherms) were essential in order to understand the phenomena related to proposed emulsification process. Multiple emulsion analyses (macroscopic, microscopic, size distribution, pH and zeta potential values, relative viscosity, rheological profile and macromolecule addition influence) were carried out. Production and emulsification temperatures (78±2grausC) were fundamental parameters in order to obtain multiple droplets by one step. Their macro and microscopic aspects were completely conditioned by the emulsification temperature. The sizes of the multiple droplets obtained were significantly smaller than those reported in the literature. For the critical temperature range, the minimum surface tension values were reached. Surface elasticity results suggest that the behavior of the surfactant molecules, in association or not, was fundamentally influenced by the temperature. Increasing surfactant molecule moieties on the surface, the intra molecular interactions were misplaced. The Langmuir isotherm as a function of the temperature demonstrated distinctive behavior for the critical temperature range, where the transition phase into solid state and soon afterwards some collapse could be observed. This phenomenon indicated some dramatic alteration of the surface film microstructure. The encapsulation process was regarded as efficient. The release profile studies demonstrated that the dispersed system in analysis was not ready yet for this research stage. The proposed emulsification process was able to produce multiple droplets by one step; moreover this result presented direct influence of the surfactant physical chemistry features, particularly the hydrophilic one, castor oil derivate, and of the methodology employed. The abnormal, non-occasional and non-transitory, multiple emulsion formation suggest a combination of transitional (ethoxylated non ionic surfactant influence), and catastrophic (dispersed/dispersant ratio influence) phase inversion processes. The obtained multiple emulsions presents microstructure aspects were not easily reproducible; however those were regarded stable for the analysis methodology employed.
|
Page generated in 0.1176 seconds