31 |
Structuration et contrôle de l’architecture de capsules à coeur liquide à base d’hydrogel d’alginate par association de biopolymères / Structuring and control of the architecture of alginate liquid-core capsules by biopolymers associationBen Messaoud, Ghazi 29 October 2015 (has links)
Cette thèse a pour objectif d’étudier les propriétés physico-chimiques de capsules à cœur liquide à base d'hydrogel d'alginate et de contrôler leur perméabilité et propriétés mécaniques par ajout des biopolymères. Ces capsules sont préparées par un procédé de sphérification inverse par extrusion goutte à goutte d’une solution de chlorure de calcium dans un bain à base d’alginate. Dans un premier travail, l’influence des polymères utilisés pour contrôler la viscosité du cœur liquide lors de la préparation des capsules sur la perméabilité et la stabilité mécanique a été étudiée. Les propriétés mécaniques des capsules ont été corrélées avec les propriétés viscoélastiques d’hydrogels d’alginate caractérisés par rhéologie oscillatoire aux faibles amplitudes. Un second travail, a consisté à élaborer des capsules composites avec une membrane de caséinate de sodium/alginate qui présentent une meilleure stabilité et une libération pH-dépendante d’un colorant utilisé comme molécule modèle. Comme perspective a cette étude, des hydrogels sphériques à base d’alginate et de caséinate de sodium, avec différentes architecture ont été développés et leur efficacité a été testée sur trois colorants. Enfin, l’influence de l’incorporation de la gomme laque dans la membrane ou comme revêtement externe a permis de mettre en évidence une amélioration des propriétés barrières vis-à-vis de molécules de faible masse moléculaire (riboflavine dans ce cas). Les capsules à base d’alginate ont un large spectre d’utilisation allant de la cuisine moléculaire à la biotechnologie ce qui nécessite une meilleure compréhension et contrôle de leurs propriétés physicochimiques en fonction de l’application visée / The aim of this thesis is to study the physicochemical properties of alginate liquid-core capsules and to control their permeability and mechanical properties by biopolymers blending. These millimeter-scale size capsules are prepared by a reverse spherification process by dripping a solution of calcium chloride into an alginate gelling bath. In a first work, the influence of polymers used to control capsule liquid-core viscosity (thickening agent) during capsules preparation on permeability and mechanical stability of the alginate membrane was investigated. The mechanical properties of capsules were correlated with viscoelastic properties of plane alginate hydrogels characterized by small amplitude oscillatory shear rheology. In a second work, composite capsules with a membrane of sodium caseinate / alginate were developed and showed improved stability and pH-dependent release of a dye used as a model molecule. As a perspective, composite alginate/sodium caseinate microspheres with different architectures were developed and their effectiveness was tested against three anionic dyes. This type of system has applications in the removal of dyes from industrial wastewater by an adsorption mechanism. Finally, the influence of shellac incorporation in alginate membrane or as an external coating layer resulted in enhanced physicochemical properties and decreased membrane permeability against low molecular weight molecules (riboflavin in this case). Alginate capsules have a wide range of applications ranging from molecular gastronomy to biotechnology which requires a better understanding and control of their physicochemical properties according to the target application
|
32 |
Stabilization and development of sustained-release formulations of protein/antibody for subcutaneous deliveryMarquette, Sarah 11 September 2014 (has links)
ABSTRACT<p><p>This project aimed at developing a drug delivery system (DDS) able to enhance the stability and<p>residence time in vivo of antibodies (Abs). The system will deliver drug by the subcutaneous<p>route (SC), while ensuring accurate control of the drug release and the resulting plasmatic level. This technology platform will allow to reduce frequency of injection, potentially decrease side effects and maintain high concentration of Abs which will improve life of patient having chronic disease such as autoimmune and inflammatory disease. Biodegradable synthetic polymer-based formulations (polylactide-co-glycolide (PLGA)) were selected as carriers for encapsulated Abs. This was because they offer good protection for the Abs and allow sustained release of the Abs for a controlled period of time. After the evaluation of different encapsulation methods such as the water-oil-in-water (w/o/w) and the solid-in-oil-inwater<p>(s/o/w) processes, the encapsulation of the Ab in solid state (s/o/w) appeared to be more appropriate for producing Ab-loaded PLGA microspheres (MS). It allowed us to maintain the<p>Ab in a monomeric conformation and to avoid the formation of unsoluble aggregates mainly present at the water/oil interface. The first part of the project was the optimization of both the method for producing the Ab solid particles (spray-drying process) and the encapsulation of these Ab solid particles into the polymeric MS (s/o/w process) by design of experiment (DoE). These optimizations were carried out using a bovine polyclonal immunoglobulin G (IgG) as model molecule. In further optimization of the spray-drying process by (DoE), aqueous Ab solutions were spray-dried using a mini Spray-Dryer assembly with a 0.7 mm spray nozzle. In accordance with the particle size (d(0.5) ~5 μm), the stability (no loss of monomer measured by<p>size exclusion chromatography (SEC) and the yield of the spray-drying process (> 60 % w/w), the process parameters were set of follow: 3 mL/min as liquid feed flow rate, 130°C /75°C as inlet temperature (inlet T°) / outlet temperature (outlet T°), 800 L/h as atomization flow rate and<p>30 m3/h as drying air flow rate. For the s/o/w, the methylene chloride (MC) commonly used for<p>an encapsulation process was replaced by ethyl acetate (EtAc), which was considered as a more<p>suitable organic solvent in terms of both environmental and human safety. The effects of several processes and formulation factors were evaluated on IgG:PLGA MS properties such as: particle size distribution, drug loading, IgG stability, and encapsulation efficiency (EE%). Several formulations and processing parameters were also statistically identified as critical to get reproducible process (e.g. the PLGA concentration, the volume of the external phase, the emulsification rate, and the quantity of IgG microparticles). The optimized encapsulation<p>method of the IgG has shown a drug loading of up to 6 % (w/w) and an encapsulation efficiency<p>of up to 60 % (w/w) while preserving the integrity of the encapsulated antibody. The produced MS were characterized by a d(0.9) lower than 110 μm and showed burst effect lower than 50 %(w/w). In the second part of the project, the optimized spray-drying and s/o/w processes<p>developed with the IgG were applied to a humanized anti-tumor necrosis factor (TNF) alpha<p>MAb to confirm the preservation of the MAb activity during these processes. The selected s/o/w method allowed us to produce MAb-loaded PLGA MS with an appropriate release profile up to 6 weeks and MAb stability. In order to maintain the Abs’ activity, both during encapsulation and<p>dissolution, the addition of a stabilizer such as trehalose appeared to be crucial, as did the<p>selection of the PLGA. It was demonstrated that the use of a PLGA characterized by a 75:25<p>lactide:glycolide (e.g. Resomer ® RG755S) ratio decreased the formation of low molecular weight species during dissolution, which led to preserve Abs activity through its release from the<p>delivery system. Furthermore, the release profile was adjusted according to the type of polymer<p>and its concentration. E.g. 10 % w/v RG755S allowed Ab MS with a release time of 6 weeks to<p>be obtained. The optimization of both the formulation and the encapsulation process allowed<p>maximum 13 % w/w Ab-loaded MS to be produced. It was demonstrated that the Ab-loaded PLGA MS were stable when stored at 5°C for up to 12 weeks and that the selection of the appropriate type of PLGA was critical to assuring the stability of the system. The better stability observed when using a PLGA characterized by a 75:25 lactide:glycolide ratio was attributed to<p>its slower degradation rate. Finally, the sustained release of Ab from the developed MS and the preservation of its activity was confirmed in vivo in a pharmacokinetic (pK) study realized in<p>rats. In conclusion, the application of the concept of entrapment into a polymer matrix for<p>stabilization and sustained release of biological compounds was demonstrated through this work.<p><p><p><p>RÉSUMÉ<p><p>Ce projet a pour but de développer un système de délivrance de médicament capable d’augmenter la stabilité et le temps de résidence in vivo des anticorps. Ce système sera administré par voie sous-cutanée et permettra un control précis de la libération du produit et de son niveau plasmatique. Cette plateforme technologique nous permettra de réduire la fréquence d’injection, de réduire potentiellement les effets secondaires et de maintenir des concentrations élevées en anticorps tout en améliorant la vie des patients atteints de maladies chroniques autoimmunes ou inflammatoires. Les formulations à base de polymères synthétiques, biodégradables (PLGA) ont été sélectionnés comme véhicules pour encapsuler les anticorps. Ils offrent en effet une bonne protection pour les anticorps and permettent une libération contrôlée de ceux-ci pendant une période définie. Après l’évaluation de différents méthodes d’encapsulation tels que les procédés d’eau-dans-huile-dans-eau (w/o/w) et solide-dans-huile-dans-eau (s/o/w), l’encapsulation des anticorps sous forme solide apparaissait plus apporpriée pour produire des microsphères de polymère chargées en anticorps. Cette technique nous permettait de maintenir l’anticorps sous sa forme monomérique et d’éviter la formation d’agrégats insolubles qui apparaissaient principalement à l’interface eau/huile. La première partie du projet a été d’optimiser à la fois la méthode nous permettant d’obtenir les anticorps sous forme de particules solides (spray-drying) et la méthode d’encapsulation de ces particules d’anticorps dans les microsphères de polymères. Cela a été réalisé par des plans d’expérience en utilisant une IgG bovine polyclonale comme molécule modèle. Durant l’optimisation du procédé de spray-drying,<p>les solutions aqueuses d’anticorps ont été atomisées en utilisant le mini Spray-Dryer assemblé avec une buse de pulvérisation d’un diamètre de 0.7 mm. En accord avec la taille particulaire (d(0.5) ~5 μm), la stabilité (absence de perte en monomère mesurée par chromatographie d’exclusion de taille et le rendement d’atomisation (> 60 % w/w), les paramètres d’atomisation ont été fixés: 3 mL/min pour le débit de liquide, 130°C /75°C pour la température d’entrée / température de sortie, 800 L/h pour le débit d’air d’atomisation et 30 m3/h pour le débit d’air de séchage. Pour le s/o/w, le dichlorométhane communément utilisé dans les procédés d’encapsulation a été remplacé par l’acétate d’éthyle qui est considéré comme un meilleure solvant organique en terme d’environnement et de sécurité. Les effets de plusieurs paramètres de fabrication ou de formulation ont été évalués sur les propriétés des microsphères polymériques d’anticorps (distribution de taille particulaire, taux de charge en anticorps, stabilité de l’anticorps et efficacité d’encapsulation). Plusieurs paramètres de fabrication et de formulation ont été statistiquement identifiés comme critiques pour obtenir un procédé reproductible (par exemple. La concentration en PLGA, le volume de phase externe, la vitesse d’émulsification et la quantité d’anticorps). La méthode d’encapsulation ainsi optimisée permettait d’obtenir un taux<p>de charge jusqu’à 6% (w/w) avec une efficacité d’encapsulation jusqu’à 60 % (w/w) tout en<p>préservant l’intégrité de l’anticorps encapsulé. Les microsphères produites étaient caractérisées<p>par un d(0.9) inférieur à 110 μm et montraient une libération après 24 h inférieure à 50 % (w/w).<p>Dans le seconde partie du projet, les procédés d’atomisation et d’encapsulation développés avec<p>l’IgG ont été appliqués à un anticorps monoclonal anti-TNF alpha humanisé pour confirmer la<p>conservation de l’activité de l’anticorps pendant ces procédés. La méthode s/o/w sélectionnée<p>permettait de produire des microsphères de PLGA chargées en anticorps avec un profil de libération jusqu’à 6 semaines et un maintien de la stabilité de l’actif. Afin de maintenir l’activité de l’anticorps, à la fois pendant le procédé d’encapsulation et pendant la libération, l’ajout d’un stabilisant tel que le tréhalose est apparu crucial ainsi que le choix du type de PLGA. Il a été démontré que l’utilisation du PLGA caractérisé par un ratio lactide :glycolide de 75 :25 (par exemple, Resomer ® RG755S) diminuait la formation d’espèces de faible poids moléculaire<p>pendant la dissolution. Cela contribuait à préserver l’activité de l’anticorps durant la libération à partir des microsphères. De plus, le profil de libération était modulé en fonction du type de polymère et de sa concentration. Par exemple, l’utilisation d’une solution à 10 % w/v RG755S conduisait à la production de microsphères d’anticorps avec un temps de libération sur 6<p>semaines. L’optimisation de la formulation et du procédé d’encapsulation a permis de produire<p>des microsphères avec des taux de charge en anticorps de maximum 13 % w/w. Il a été démontré<p>que ces microsphères, stockées à 5°C, étaient stables jusqu’à 12 semaines et que la sélection du<p>type de PLGA était critique pour assurer la stabilité du système. La meilleure stabilité a été<p>obtenue en utilisant le PLGA caractérisé par un ratio lactide :glycolide de 75 :25. Cela a été<p>attribué à sa plus faible vitesse de dégradation. Enfin, la libération contrôlée de l’anticorps à<p>partir de ces microsphères et la conservation de son activité ont été confirmées in vivo lors d’une<p>étude pharmacocinétique réalisée chez le rat. En conclusion, ce travail a permis de démontrer<p>l’application du concept d’ « emprisonnement » des composés biologiques dans des matrices<p>polymériques afin de les stabiliser et contrôler leur libération. / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished
|
33 |
Supramolecular interactions from small-molecule selectivity to molecular capsulesRajbanshi, Arbin January 1900 (has links)
Doctor of Philosophy / Department of Chemistry / Christer B. Aakeroy / Supramolecular synthesis relies upon the creative and rational use of the common intermolecular forces and a proper understanding of these forces is critical for design and assembly of molecular building blocks into extended networks. The strength of seven substituted pyridines as hydrogen-bond acceptors was probed using a series of fifteen mono/dicarboxylic acids to demonstrate the interrelationship between the charge on the substrate and its ability to form co-crystals/salts. The higher charge in the acceptor led to proton transfer (100% yield) from the hydrogen bond donor to give a salt, whereas the lower charge led to co-crystals. This specificity observed for small molecules was extended to an investigation of selectivity in ditopic molecules. A series of nineteen hydrogen-bond donors, including fifteen carboxylic acids and four cyanoximes, were tested for binding preferences against ten ditopic ligands with variable charges. The overall supramolecular yield of 82% (9/11) proved a high degree of reliability in terms of best acceptor/donor approach, hence establishing the efficiency of the calculated charges as a guideline for molecular recognition processes.
Solubility and thermal properties of pharmaceutical drug mimics were altered via formation of co-crystals/salts. The ligands and their co-crystals/salts with five even-chain dicarboxylic acids were synthesized and their comparative solubility in pure water and in pH 6.8 buffer solution measured. Solubility enhancement to a degree of 9x is observed for pharmaceutical drug haloperidol, whereas decrease in solubility down to 81% is achieved for 2-amino-5-(3-pyridyl)pyrimidine (which has agrochemical significance). Also the thermal and solubility behavior of these co-crystals were shown to reflect the properties of their parent co-crystallizing agents, allowing for a modulation of physical properties.
Finally, the specificity and selectivity of the intermolecular interactions observed for small molecules were applied in the synthesis of hydrogen and halogen-bonded capsules. Several resorcinarene-based cavitands were synthesized and their upper rim decorated with acetamidopyridyl, aminopyrazinyl, 3-pyridyl, and 4-pyridyl moieties with hydrogen and halogen-bonding potentials. A homomeric hydrogen-bonded capsule was formed with self-assembly of acetamidoethynylcavitand via N-H···O=C interactions, whereas a heteromeric halogen-bonded capsule, the very first of its kind, was formed with N···I halogen-bonded interaction between 3-pyridylcavitand and tetrafluoroiodo-substituted calixarene.
|
34 |
Classifying Objects from Overhead Satellite Imagery Using CapsulesDarren Rodriguez (6630416) 11 June 2019 (has links)
<div>Convolutional neural networks lie at the heart of nearly every object recognition system today. While their performance continues to improve through new architectures and techniques, some of their deciencies have not been fully addressed to date. Two of these deciencies are their inability to distinguish the spatial relationships between features taken from the data, as well as their need for a vast amount of training data. Capsule networks, a new type of convolutional neural network, were designed specically to address these two issues. In this work, several capsule network architectures are utilized to classify objects taken from overhead satellite imagery. These architectures are trained and tested on small datasets that were constructed from the xView dataset, a comprehensive collection of satellite images originally compiled for the task of object detection. Since the objects in overhead satellite imagery are taken from the same viewpoint, the transformations exhibited within each individual object class consist primarily of rotations and translations. These spatial relationships are exploited by capsule networks. As a result it is shown that capsule networks achieve considerably higher accuracy when classifying images from these constructed datasets than a traditional convolutional neural network of approximately the same complexity.</div>
|
35 |
Influência de adjuvantes sobre as características farmacêuticas de cápsulas de gelatina dura contendo hidroclorotiazidaGuterres, Silvia Stanisçuaski January 1990 (has links)
A biodisponibilidade é uma característica decisiva para a eficácia dos medicamentos, podendo sua intensidade ser estimada através da cedência "in vitro". Vários fatores são capazes de influenciá-la, entre eles a composição quali e quantitativa dos adjuvantes, assim como as características da substância ativa e da forma farmacêutica. A hidroclorotiazida é um diurético de amplo emprego, que apresenta problemas de biodisponibilidade e bioequivalência devido a sua baixa hidrossolubilidade. Através de planejamento fatorial 2 3 foram preparadas formulações de cápsulas de gelatina dura contendo 50 mg de hidroclorotiazida. Foi analisada a influência dos fatores material de enchimento (lactose e celulose microcristalina), reguladores de fluxo (dióxido de silício altamente disperso e estearato de magnésio) e hidrofilizante (polissorbato 80) sobre as características de qualidade dos complexos farmacêuticos e das cápsulas. O regulador de fluxo ou a interação entre este e o material de enchimento foram os fatores determinantes nas características de fluxo dos complexos farmacêuticos, analisadas através do ângulo de repouso e do índice de compressibilidade. A cedência "in vitro" das cápsulas, determinada com auxílio de aparelho de célula de fluxo e parametrizada pela eficiência de dissolução, foi influenciada preponderantemente pelo regulador de fluxo. Foram comparados os perfis de cedência "in vitro" entre as cápsulas e comprimido do mercado. O comportamento intermediário demonstrado pelo comprimido indica a necessidade de avaliação comparativa entre medicamentos contendo hidroclorotiazida a fim de assegurar sua bioequivalência. / The bioavailability is a decisive characteristic to drugs efficacy that can be predict by different "in vitro" dissolution methods. The bioavailability has been shown to be dependent on factors such as the drug, the dosage forms, type and quality of adjuvants. Hydrochlorothiazide is a widely used diuretic. Due to its limited aqueous solubility, this drug has potencial bioavailability problems. Eight differents hydrochlorothiazide hard gelatin capsules, containing 50 mg of the drug, were prepared according to a 2 3 factorial design. The influence of fillers (lactose or microcrystaline cellulose), glidants (magnesium stearate or coloidal silicon dioxide) and surfactant (polysorbate 80) on the pharmaceutical characteristics of powder mixtures and capsules were evaluated. The powder mixtures flow characteristics were evaluated through repose angle and compressibility index. It was determined that the glidant and its interaction with filler influenced this characteristic. The "in vitro" release of hydrochlorothiazide from capsules was carried out by a open flow-though dissolution method. The dissolution efficiency was the selected parameter to express the drug release. The glidant was the determinant factor. The dissolution profile of these capsules and marketed tablets was compared. The results evidenced the importance of comparative evaluation of hydrochlorothiazide dosage forms to assure their bioequivalence.
|
36 |
Células tronco mesenquimais de muares inclusas em microcápsulas de hidrogel de alginatoSouza, Jaqueline Brandão January 2019 (has links)
Orientador: Ana Liz Garcia Alves / Resumo: As terapias regenerativas com a utilização de células tronco mesenquimais (CTMs) têm sido amplamente empregadas com a finalidade de modificar a progressão de enfermidades locomotoras em animais de grande porte. Estudos sobre o comportamento das células tronco, portanto, mostram-se de extrema importância para que, cada vez mais, elucidar sua ação, efeito e eficácia nos tratamentos propostos. A inserção das CTMs derivadas do tecido adiposo de muares em microcápsulas de hidrogel gera expectativas promissoras para a proteção da célula contra anticorpos do receptor, bem como processos inflamatórios exacerbados, distribuição de agentes terapêuticos e supressão de processos inflamatórios. O presente trabalho teve por objetivo verificar o comportamento das CTMs após o encapsulamento em hidrogel, quanto a sua viabilidade, migração, além da avaliação morfológica e imuno-histoquímica. Avaliação da morfologia da cápsula, dos poros, a rugosidade por microscopia eletrônica de varredura (MEV) e observação das células encapsuladas pela microscopia confocal de varredura a laser. A porcentagem de células viáveis manteve-se ao longo dos momentos em uma média de 93%, então o biomaterial permitiu a difusão de nutrientes e oxigênio adequadamente. A diminuição da quantidade de células no interior das cápsulas é justificada pela possível migração das mesmas através dos microporos das microcápsulas permitindo a aderência à placa de cultivo. Na avaliação morfológica foi possível identificar as células... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Regenerative therapies using mesenchymal stem cells (MSCs) have been widely widespread to treat locomotor diseases in large animals. Studies on the behavior of stem cells are extremely important to increase our knowledge regarding their action, effect and effectiveness in the proposed treatments. The insertion of muar adipose-derived MSCs into hydrogel microcapsules yields promising expectations for cell protection against immune response, as well as exacerbated inflammatory processes, delivery of therapeutic agents, and suppression of inflammatory processes. The present research aimed to verify the behavior of MSCs after hydrogel encapsulation, including cell viability, migration, morphological and immunohistochemical pattern. Evaluation of capsule morphology, pore size, roughness by scanning electron microscopy (SEM) and observation of encapsulated cells by confocal laser scanning microscopy. The percentage of viable cells remained throughout the moments at an average of 93%, so the biomaterial allowed the diffusion of nutrients and oxygen properly. A decreased amount of cells number inside the capsules is justified by the possible migration of them through the microcapsule micropores allowing adherence to the culture plate. The cells showed positive CD44 staining, absence in MHC II. The capsules were evaluated with SEM for their morphology, the area of circular and irregular pores and the size of the cells. It was possible to confirm the presence of stem cells in the micro... (Complete abstract click electronic access below) / Doutor
|
37 |
An evaluation of food gums for encapsulating enzymes to accelerate cheese ripeningLam, Henry, University of Western Sydney, Hawkesbury, Faculty of Science, Technology and Agriculture, School of Food Science January 1997 (has links)
Selected food gums (hydrocolloids) were tested for their abilities to encapsulate enzymes for acclerating cheese ripening. The effect of pH and acidity on gel strength of the gums was determined. Enzyme was entrapped in k-carrageenan, gellan gum and milk fat and incorporated into cheese milk prior to cheese making. The cheese produced was tested for protein breakdown and amino acid production during ripening and textural and sensory properties of the ripened cheese were also evaluated. The findings and significance of this study and the literature review are presented. Gels were produced from alginate. Most gels showed reduced strength after treatment in solutions of either modified acidities or pH. There was, however, no significant change in gel strength between the different treatments for most of the gums. The activity of encapsulated enzyme were also investigated. Enzymes encapsulated in k-carrageenan, gellan and alginate gums retained higher activities than the other gums studied. Enzymes entrapped in agar gels had the least retention of activity. The retention of enzyme capsules produced from gellan, k-carrageenan and milk fat in cheese curd was investigated. Loss of encapsulated enzymes in cheese whey was also determined. Enzyme loss in the whey ranged from 5.6 to 17.9% with the highest losses observed with milk fat and the least with gellan gum capsules. Most of the cheeses treated with enzyme capsules showed higher levels of amino acid within two weeks than control cheese. After two weeks, all experimental cheeses showed higher production of amino acids than the control cheese. The addition of enzyme capsule to cheese did lead to a higher growth level of microorganisms. The experimental cheese exhibited lower score than the control cheese for most textural properties. The experimental cheeses were not significantly different in flavour and aroma from the control cheese. K-carrageenan treated cheeses were recorded as having the highest score for bitter after taste. Except for those cheeses treated with k-carrageenan capsules, the overall acceptability for the trial cheeses were not significantly different from that of 6 month old untreated cheese. / Master of Science (Hons)
|
38 |
Couplage intégrales de frontières – éléments finis : application aux capsules sphériques et ellipsoïdales en écoulement.Walter, J. 03 December 2009 (has links) (PDF)
Une capsule est une goutte liquide entourée d'une fine membrane élastique. La modélisation du comportement mécanique d'une capsule est un problème complexe de couplage entre la mécanique des fluides interne et externe et celle de la paroi de la capsule, qui peut subir des grandes déformations. On a développé une nouvelle méthode numérique pour modéliser le comportement d'une capsule dans un écoulement de Stokes infini. Le problème fluide est résolu à l'aide de la méthode des intégrales de frontière, tandis que la problème solide l'est par des éléments finis de membrane. La stratégie de couplage développée est non-classique, en particulier parce que les déplacements (plutôt que les efforts) sont imposés aux éléments finis de membrane. Cette nouvelle méthode est conditionnellement stable, précise et demeure stable en présence de compression dans le plan de la membrane, ce qui est une situation qui pose problème avec d'autres méthodes. On applique cette méthode à l'étude de capsules de forme initiale ellipsoïdale, dans un écoulement de cisaillement simple infini. Ces capsules ont des applications biomédicales intéressantes, et constituent un premier modèle mécanique de globule rouge. On met en évidence deux régimes distincts, selon l'intensité du cisaillement dans le fluide : le tumbling (quasi-solide) et le swinging (quasi-fluide). On montre également que les propriétés de la paroi (loi de comportement, module de dilatation surfacique) ont une influence cruciale sur le comportement de la capsule. La nouvelle méthode numérique est prometteuse et peut être étendue pour prendre en compte un rigidité de flexion de la paroi.
|
39 |
Pharmaceutical evaluation of phela capsules Used as traditional medicineSehume, Brian J. January 2010 (has links)
<p>In conclusion, the results obtained firstly indicated that the BP, EMEA and WHO were in fairly good agreement on the criteria and specifications that can be used to assesses the pharmaceutical quality of a traditional plant medicine such as Phela. Secondly, the Phela plant powders were found to have acceptable pharmaceutical properties that did not complicate or adversely affected the capsule manufacture. Thirdly, the Phela capsules produced were generally of acceptable pharmacopoeial standard. Fourthly, HPLC fingerprinting and pattern recognition analysis proved useful to examine the chemical stability of selected marker compounds of Phela and indicated that the capsules had no practical shelf life under elevated temperature and humid conditions. Overall, the Phela capsules should thus be suitable for use in a short time clinical trial, but for use in a long period trial the long term stability of the Phela capsules under ambient conditions must still be confirmed.</p>
|
40 |
Intelligent Microcontainers : Fabrication, Characterization And Tunable Release Properties For Drug DeliveryAnandhakumar, S 07 1900 (has links) (PDF)
Polyelectrolyte capsules fabricated by layer-by-layer (LbL) technique are introduced as a simple and efficient carrier system for spontaneous deposition of proteins and low molecular water soluble drug. The objective of the work was to investigate the applicability of polyelectrolyte capsules as vehicles for sustained or controlled delivery of drugs. Two different polymeric systems composed of weak and strong polyelectrolytes were chosen to study the loading and release behavior in order to meet the requirements of biomedical applications.
In the first system, the wall permeability of weak polyelectrolyte (PAH/PMA) capsules could be readily manipulated from open to closed state by simply varying the pH. The open and closed state of the capsules could be attributed to the charge density variation of weak polyelectrolytes, which induces the capsule wall to undergo a transition from continuous to nanoporous morphology due to phase segregation. Bovine Serum Albumin (BSA) was spontaneously deposited in the hollow capsules and deposition was investigated by CLSM, SEM and AFM techniques. The driving force for spontaneous deposition was electrostatic interaction between the preloaded polystyrene sulfonate (PSS) and BSA. The deposition was uniform and concentration of BSA in the capsule interior reached a few hundred times greater than that of bulk. The amount of loading was significantly influenced by the loading pH, loading concentration and charge density of substance to be loaded at the corresponding pH. The deposition was successful up to the isoelectric point of BSA (pH = 4.8) and there was no loading observed above that, since the deposition is based on electrostatic attraction between PSS and BSA. During the release at physiological pH of 7.4, charge reversal of BSA occurred which induced electrostatic repulsion between PSS and BSA thereby triggering the movement of BSA from the interior to the bulk. Release continued up to 5 h in water and a total release of 63 % was observed which increased to 72 % when release was performed in PBS.
Spontaneous deposition of low molecular weight, water soluble drug, ciprofloxacin hydrochloride was performed in the same manner and its release profile was studied. Controlling diffusion of smaller drug molecules is extremely difficult in drug delivery applications. Cross linking of capsule wall components could be used to control the release rates of smaller drug molecules. Cross linking density is dependent on the cross linking time and increases the stiffness of the capsule wall. Release of ciprofloxacin hydrochloride was possible even up to 6 h after cross linking. Antibacterial studies showed that the drug released even after 25 h has a significant effect on the bacterial pathogen E.coli.
The second system included weak and strong polyelectrolytes (PAH & DS) and a novel route was employed to fabricate optically addressable capsules that could be laser activated for delivery of drugs. This approach involved a combination of LbL assembly and polyol reduction method wherein PEG was used to reduce AgNO3 to Ag nanoparticles (NPs). The capsules were prepared via LbL assembly of PAH and DS on silica template followed by synthesis of silver NPs in the layers and subsequent dissolution of the silica core. The sulfonate groups of DS present in the polyelectrolyte film act as binding sites for the adsorption of silver ions which are then reduced to silver NPs in the presence of PEG. The size of the silver NPs formed was influenced by the AgNO3 concentration used. At lower concentration, smaller particles of uniform distribution were observed which turned into larger particles of random distribution when the concentration of AgNO3 is increased. Silver NPs embedded capsules ruptured when exposed to laser and was significantly influenced by silver NPs size, their distribution, laser intensity and time of exposure. The synthesis of silver NPs increased the permeability of the capsules to higher molecular weight substances like dextran caused by the defects, discontinuities and pores created on the polymeric network due to the newly formed silver NPs. Encapsulation of FITC-dextran was performed using thermal encapsulation method by exploiting temperature induced shrinking of the capsules at elevated temperatures. During heat treatment the porous morphology transformed into smooth pore free structure which prevented the movement of dextran into the bulk and hence enrichment inside the capsules. The loaded dextran was readily released when exposed to laser and the release could be controlled from linear to burst release in order to meet practical requirements in biomedical applications.
|
Page generated in 0.027 seconds