Dissertations / Theses on the topic 'Alginic acid'

A sustainable approach focused on the practice of green chemistry was used to develop a method which improved the performances of a catalyst system based on a natural and non-toxic substance. A benchmark Michael addition reaction was performed employing 9-amino(9-deoxy)epi quinine, adsorbed on alginic acid gels by hydrogen bonds, as catalyst. Compared to conventional heterogeneization of this organic catalyst, the present approach is more straightforward and employs as support a renewable biomaterial instead of oil-derived polymers. The optimization of the adsorption protocol was carried out to obtain an active and heterogeneous system able to work under different reaction temperatures. The Michael addition reaction rate, heterogeneity, enantiomeric excess and recyclability of the catalytic system were studied. The influence of temperature, additives and the presence of water were successfully investigated. The heterogeneity of the catalyst was perfectly preserved, therefore the catalyst could be easily recovered. Two optimal conditions were disclosed, differing in reaction temperature and catalyst pre-treatment. A scale-up is performed with good results for the first three reactions cycles (conversions: 100%, 87% and 55% respectively). The enantiomeric excess is determined as 98%. The results of this project demonstrated that a green catalytic system has a great potential to be competitive with more classic heterogeneous catalysts.

This study investigated the thermal decomposition of two structurally similar polysaccharides – cellulose and alginic acid, arguably being the two largest sources of biomass on land and from the sea respectively. Despite the similarity in the two materials and applications, reviewing literature of the combustion and pyrolysis mechanisms of the two materials showed a relatively well-established framework of knowledge for cellulose, although there is still some lack of agreement in some areas. This contrasted with the almost total absence of any information on the thermal behaviour of alginic acid. The aim of the work reported in this thesis was to use the structural similarities and the mechanistic framework for cellulose to conduct a comparative investigation of the two materials. Taking advantage of high throughput multivariate algorithms to process complex spectroscopic data produced by TGA-FTIR, a method was developed to identify infrared active volatile species generated above a detectable threshold during the thermal degradation process. The ability to plot an evolution profile of a selected compound in time- and/or temperature domain significantly enhanced the capabilities of a standard TGA-FTIR system for mechanistic investigations. With the technique established, the two materials were analysed under different heating rates (5, 10, 30, 60°C/min) under nitrogen and again under 10% oxygen in nitrogen. A reconstruction of the cellulose decomposition pathway was carried out using the data obtained from this work. Compared to the methods available in the scientific literature, the current method was a simpler and more efficient technique for providing information related to the thermal degradation behaviours of the sample materials. The application of the method to alginic acid revealed for the first time that this material responded differently and more sensitively to the presence of oxygen than did cellulose. Its decomposition pathway has a number of distinctive steps, in contrast to cellulose.

ABSTRACT BIOSENSOR BASED ON INTERPENETRATED POLYMER NETWORK OF ALGINIC ACID AND POLY (1-VINYLIMIDAZOLE) Kartal, Mü
jgan M.S., Department of Chemistry Supervisor : Prof. Dr. Levent Toppare January 2008, 63 pages A new proton conductor polymer was prepared using alginic acid (AA) and poly (1-vinylimidazole) (PVI). The polymer network was obtained by mixing AA and PVI at various stoichiometric ratios, x (molar ratio of the monomer repeat units). The AA/PVI network was characterized by elemental analysis (EA) and FT-IR spectroscopy. Potential use of this network in enzyme immobilization was studied. Enzyme entrapped polymer networks (EEPN) were produced by immobilizing invertase and tyrosinase (PPO) in the AA/PVI network. Additionally, the maximum reaction rate (Vmax) and Michaelis-Menten constant (Km) were investigated for the immobilized invertase and enzymes. Also, temperature and pH optimization, operational stability and shelf life of the polymer network were examined.

By mixing different stoichiometric ratios of chitosan with alginic acid (AA) and chitosan with p(toluenesulfonicacid) (PTSA), two new polymer networks were prepared. FT-IR spectroscopy results show the protonation of chitosan by AA and PTSA. Elemental analysis (EA) results show the composition of the networks. Thermal gravimetry analysis (TGA) and differential scanning calorimetry (DSC) results were used to characterize the thermal stability of the networks. Then, cholesterol oxidase (ChOx) enzyme were immobilized in these networks and checked for potential use of these enzyme entrapped polymer networks (EEPN) for enzyme immobilization. Additionally, the maximum reaction rate (Vmax) and Michaelis-Menten constant (Km) were evaluated for immobilized ChOx in these two polymer networks. Also, temperature and pH optimization, operational stability, shelf-life and the proton conductivity of these networks were investigated.

Os alginatos de metais alcalinos (Li+, Na+ e K+), alcalino-terrosos (Mg2+, Ca2+, Sr2+ e Ba2+), de amônio, mono-, di- e trietanolamônio foram sintetizados por neutralização do ácido algínico com os respectivos hidróxidos, ou carbonatos, e com as aminas. Os sais foram caracterizados por análise elementar e espectroscopia na região do infravermelho, confirmando as sínteses. Após caracterização, os compostos foram submetidos à análise térmica (TG/DTG, DTA e DSC) para avaliar seu comportamento térmico e seus resíduos de decomposição, que foram caracterizados por IR e XRD. Os alginatos de amônio e etanolamônio se decompuseram com liberação de amônia ao final do experimento. Os alginatos de metais alcalinos foram convertidos nos seus respectivos carbonatos, enquanto os alginatos de metais alcalino-terrosos se decompuseram formando carbonatos, em seguida óxidos. Foi feita uma avaliação de procedimentos de secagem por estufa a vácuo a 40 ºC e liofilização; e o último método mostrou-se mais eficaz. A água residual, não-congelável, sai associada à decomposição do material e não foi possível definir exatamente seu teor. Um método de medir o grau de substituição nos sais das aminas foi desenvolvido com base em 13C ? NMR em fase sólida.
The alkaline (Li+, Na+ and K+), earth-alkaline (Mg2+, Ca2+, Sr2+ and Ba2+), ammonium, mono-, di- and triethanolammonium alginic acid salts were obtained from the neutralization reaction between alginic acid and the respective hydroxides or carbonates, and the amines, The salts were characterized by elemental analysis and infrared spectroscopy, confirming the synthesis. After the characterization, the compounds were submitted to thermal analysis (TG/DTG, DTA and DSC), in order to evaluate their thermal behavior. The thermal decomposition residues were characterized by IR and/or XRD. The NH4+ and ethanolammonium alginates decomposed via NH3 release without residue in the crucible at the end of the experiment. The alkaline alginates were converted to the respective carbonates, and the earth-alkaline decomposed with production of the carbonates followed by convertion to the oxides. An evaluation of drying procedures involving heating under vaccum up to 40°C and lyophilization were performed, pointing better results in the last case. The residual water, of the non-freezing type, was completely released only during the decomposition of the biopolymer, and it was not possible to define its exact content in the samples. An attempt to estimate the substitution degree in the ethanolammonium salts using 13C ? NMR data, in solid state, was also described.

Foram preparados produtos da reação do ácido algínico com a monoetanolamina (MEA), dietanolamina (DEA) e trietanolamina (TEA) sob refluxo em meio de clorofórmio, os quais foram denominados MEA, DEA e TEA-produtos. Os compostos foram caracterizados por Análise Elementar e Espectroscopia Vibracional na Região do Infravermelho. As técnicas termoanalíticas Termogravimetria (TG), Termogravimetria Derivada (DTG), Análise Térmica Diferencial (DTA) e Calorimetria Exploratória Diferencial (DSC) foram utilizadas para avaliar o comportamento e estabilidade térmica, as etapas envolvidas e determinar os parâmetros cinéticos da decomposição térmica do Halg e dos produtos de reação. A 13C RMN foi utilizada para propor uma possível estrutura para o MEA-produto e também para estimar o grau de conversão de ácido a produto. A organização estrutural do Halg e de um de seus produtos de reação foi avaliada usando difração de raios X. A Microscopia Eletrônica de Varredura foi utilizada para estudar a morfologia do Halg e dos produtos de reação. O MEA-produto foi misturado aos fármacos Paracetamol, Tioconazol e Ramipril e essas misturas foram caracterizadas por Espectroscopia Vibracional na Região do Infravermelho e por Análise Térmica, com o objetivo de verificar a interação de fármacos com o material biopolimérico.
The products of the reaction between alginic acid and monoethanolamine (MEA), diethanolamine (DEA) and triethanolamine (TEA) were prepared in chlroform under reflux, named MEA, DEA e TEA-products. These compounds were characterized by Elemental Analysis and Spectroscopy in the Infrared region. The Thermal analytical techiniques Thermogravimetry (TG), Derivative Thermogravimetry (DTG), Differential Thermal Analysis (DTA) and Differential Scanning Calorimetry (DSC) were used to evaluate the thermal behavior and stability of the compounds as well as the steps and the kinetic parameters involved in the thermal decomposition of Halg and the MEA, DEA e TEA-products.
The 13C NMR was used to propose a possible structure for MEA-product and to estimate the degree of the conversion. The structure order of Halg and MEA-product was evaluated by X-ray diffraction. The scanning electron microscopy was used to investigate the morphology of Halg and the reaction products. The MEA-product was mixed with the drugs Paracetamol, Tioconazole and Ramipril. The mixtures were characterized by Infrared spectroscopy and Thermal Analysis, in order to verify the interaction of drugs with the biopolymeric material

La possibilité d’administrer des formes sèches orales est encore de nos jours un enjeu dans certaines spécialités médicales telles que la pédiatrie, la neurologie ou la gériatrie. Les mini-comprimés orodispersibles présentent un intérêt majeur pour répondre à cette problématique.L’objectif de ce travail est d’étudier les différents phénomènes qui régissent la conception de cette forme pharmaceutique par compression directe.Trois axes de recherche ont été fixés pour la réalisation de ce travail : - Premièrement, étudier les paramètres de formulation et de fabrication des mini-comprimés orodispersibles.- Deuxièmement, améliorer notre compréhension des phénomènes qui régissent la désintégration de ces comprimés au travers de l’étude du comportement de l’excipient clé de la désintégration : le super-désintégrant.- Enfin, développer un matériau à base d’acide alginique et d’alginate de calcium ayant pour fonction d’accélérer la désintégration des mini-comprimés orodispersibles.Les résultats obtenus permettent d’orienter les choix des différents excipients et les paramètres techniques pour la fabrication de cette forme. D’autre part, ils mettent en évidence le besoin de définir des spécifications et des techniques de caractérisation qui lui sont dédiées. Les résultats obtenus lors de l’étude du comportement des super-désintégrants au moment de leur hydratation, soulignent l’importance de la capacité de conduction de l’eau des super-désintégrants dans le mécanisme de désintégration des mini-comprimés orodispersibles. Enfin, les résultats des travaux réalisés pour l’obtention de matériaux super-désintégrants à base d’acide alginique permettent d’établir de premières orientations à suivre dans leurs modes de production.Les différentes conclusions issues des travaux menés lors de cette thèse permettront de valoriser cette forme pharmaceutique innovante et d’en favoriser de nouveaux développements
Patient acceptability of a medical product is a key aspect in the development of medicines. Oral administration of dry forms presents still several limitations in some medical specialties such as pediatrics, neurology or geriatrics. Orodispersible Mini Tablets (ODMTs) have been described as a potential solution to these drawbacks.In this thesis, the different parameters governing the design of these pharmaceutical forms by direct compression have been studied.Three main lines of research have been followed to carry out this work:- Firstly, the different parameters of formulation and manufacture of orodispersible mini tablets were evaluated.- Secondly, the behavior of different commercial super disintegrants, key excipents in the disintegrating action, was studied in order to improve our understanding of the phenomena governing the disintegration mechanisms of the ODMTs.- Finally, various alginate-based materials were developed and its function as super disintegrants in orodispersible mini tablets was tested.The obtained results can be used as indicatives in the choice of excipient and the technical parameters for an effective manufacture of OMDTs. Moreover, they have highlighted the need to continue defining specifications and characterization techniques dedicated to further development of OMDTs. The results obtained during the hydration studies (swelling ratio, swelling force and water uptake) of the super disintegrants underline the importance of wicking in the disintegration mechanism of the ODMT.Finally, the prepared alginate-based materials have shown to present interesting mechanical properties for the development of effective and available super disintegrants for direct compression.The choice of suitable super disintegrants for ODMTs formulation requires extensive knowledge of their properties for promoting the breakout of the tablet and of their interaction with both, water and the various materials constituting the tablet. Thus, the knowledge gained in this thesis on super disintegrant functionality will promote the appropriate development of this innovative pharmaceutical form

L’acide alginique et les alginates sont des polysaccharides biosourcés, dont la biocompatibilité, la biodégradabilité et la non-toxicité en font des matières premières largement utilisées dans le domaine médical.La présente étude s’est attachée à la valorisation et à l’analyse des performances fonctionnelles de l’acide alginique pour un usage pharmaceutique comme excipient de nouvel intérêt dans la formulation des comprimés pharmaceutiques et notamment ceux élaborés par le procédé de compression directe.Quatre axes de recherche ont guidé le déroulement de ce travail :1- L’étude de l’acide alginique en compression, en s’intéressant, d’abord au comportement propre de cette matière première lorsqu’elle est soumise à contrainte, ensuite en l’associant de façon binaire aux principaux excipients technologiques liants/diluants présents dans toute formulation de comprimé pharmaceutique et disponibles sur le marché.2- L’identification des relations structure-fonctionnalité de l’acide alginique dans la formulation de comprimés.3- Le développement d’un nouvel excipient co-processé à base d’acide alginique, pouvant présenter les caractéristiques et les performances d’un excipient dit « pour compression directe ».4- L’investigation des performances technologiques et biopharmaceutiques de ce nouveau matériau composite, en l’associant à des principes actifs modèles.Les différents résultats obtenus à travers cette étude montrent l’intérêt de l’acide alginique en tant qu’excipient de compression et mettent en évidence le lien entre les fonctionnalités et les propriétés physico-chimiques de ce polymère. Ils présentent également les différents phénomènes qui régissent le comportement mécanique de la poudre d’acide alginique en compression. Le procédé de « co-processing » conçu et développé dans le présent travail, à l’échelle du laboratoire et consistant en la mise en œuvre d’une granulation humide associant l’acide alginique à de la cellulose microcristalline, s’est avéré être une voie d’amélioration des fonctionnalités de l’acide alginique, nous permettant de disposer d’un matériau, dénommé « Cop AA-MCC » exempt de toute modification chimique, répondant ainsi à la définition même d’un excipient co-processé. Les travaux de caractérisation, d’optimisation et de formulation, menés sur ce nouvel excipient, en comparaison à des excipients commerciaux, nous permettent de conclure à son utilisation future comme nouvel excipient performant pour compression directe
Alginic acid and alginates are biosourced polysaccharides, whose biocompatibility, biodegradability and non-toxicity make them raw materials widely used in the medical field.The present study is devoted to the analysis and enhancement of the functional performance of alginic acid for pharmaceutical use as an excipient of new interest, and in particular, its application in the formulation of pharmaceutical tablets produced by direct compression process.Four research axes guided the progress of this work:1- Study of alginic acid in direct compression, by being interested, firstly in the proper behavior of this raw material when it is subjected to stress, then by associating it in a binary way with the main technological fillers/binders present in any pharmaceutical tablet formulation and available on the market.2- Identification of structure-functionality relationships of alginic acid in the formulation of tablets.3- Development of a new co-processed excipient based on alginic acid, which potentially owns the characteristics and performance of an excipient "for direct compression".4- Investigation of the technological and biopharmaceutical performance of this new composite material, by associating it with model active ingredients.The different results obtained through this study show the interest of alginic acid as a compression excipient and highlight the link between the functionalities and the physico-chemical properties of this polymer. They also present the different phenomena that govern the mechanical behavior of alginic acid powder in direct compression. The “co-processing” method designed and developed in this work, on a laboratory scale, and consisting on the association of alginic acid with microcrystalline cellulose by wet granulation, has successfully enhanced the functionality of alginic acid, yielding a material called "Cop AA-MCC" free of any chemical modification. Characterization, optimization and formulation work, carried out on this new co-processed excipient, in comparison to commercial excipients, revealed the importance of its use as a new high-performance excipient for direct compression

La industria alimentaria ha estudiado la encapsulación de compuestos bioactivos para su aplicación en el diseño de alimentos funcionales. El alginato ha sido utilizado como agente encapsulante debido a su matriz biodegradable, no tóxica y versátil que protege a éstos de las condiciones adversas del entorno, enmascara sabores y olores y, mejora su estabilidad y biodisponibilidad. En concreto, estudiar la obtención de geles de alginato como encapsulante a través de diferentes mecanismos de gelificación y técnicas derivadas para la encapsulación de compuestos activos permite determinar las condiciones más idóneas para su preparación, así como, la influencia del tipo de fuente de calcio y su concentración, pH, entre otras sobre las características viscoelásticas, tamaño, morfología y textura de los geles. Con este fin se caracteriza el alginato sódico utilizado y los geles de alginato cálcico preparados por gelificación externa (GE) y gelificación interna (GI), a partir de sus características reológicas se estudian las técnicas de encapsulación. En primer lugar, se estudian las condiciones para formar una emulsión estable que proporcione las microesferas de alginato de menor tamaño por GI, así como la encapsulación de compuestos activos polifenólicos del extracto de cacao en ellas, a través de un diseño experimental. En segundo lugar, se analizan las esferas obtenidas por extrusión con diferentes formulaciones, comparándose su tamaño, morfología y textura. También se estudia la liberación de los polifenoles desde los encapsulados hacia el medio que los rodea y el ajuste de la curva de liberación a varios modelos propuestos en la bibliografía. Finalizando con la incorporación de las esferas más idóneas según las características deseadas en un alimento para su evaluación sensorial. La estructura polimérica del alginato sódico sugiere una contribución equilibrada de sus monómeros con una distribución por bloques heterogénea que proporciona mayor flexibilidad al gel formado. Las características viscoelásticas de los geles obtenidos, en general, muestran que un incremento de la [Ca+2] proporciona geles más compactos. Las diferencias observadas entre sus propiedades indican una influencia de la fuente de calcio al utilizar GI y, del proceso de formación en el gel por GE. La distribución de tamaños de las microesferas obtenidas por GI a partir de las diferentes emulsiones y citrato cálcico indican que las microesferas de menor tamaño y polidispersidad se producen con tensioactivo polirricinoleato de poliglicerol (PGPR). Al encapsular el extracto de cacao en las microesferas, el diseño experimental muestra que la cantidad de fase dispersa influye significativamente en el porcentaje retenido de polifenoles y que la velocidad de agitación afecta al diámetro medio y la polidispersidad de las microesferas. Las esferas obtenidas por extrusión se ven afectadas por el aumento de la [Ca+2] al producirse una disminución en sus diámetros, la estructura interna de éstas confirma la influencia del tipo de gelificación, siendo las esferas obtenidas por GE heterogéneas, mientras que las formadas por GI se presentan más homogéneas. Sus propiedades texturales indican que son más duras las esferas preparadas por GE que las formadas por GI, y para todas las formulaciones que las esferas por GI son menos gomosas y, por tanto, requieren menor energía para su masticación. La liberación de los polifenoles desde los diferentes encapsulados muestra los mejores ajustes al modelo de Peppas-Sahlin, lo que sugiere una cinética dominada por la difusión del compuesto activo producto del mecanismo disolución/relajación de la matriz hinchada. La incorporación de esferas más suaves, menos gomosas con un alto contenido de extracto de cacao y [Ca+2] a un producto alimentario como la gelatina muestra a través de una evaluación sensorial que el sabor astringente y amargo del extracto natural es satisfactoriamente enmascarado.
Functional foods are beginning to play a major role in what consumers eat due that the encapsulation of active compounds is being studying by the food industry. Biopolymers as the alginate has been one of the most widely used in encapsulation due to the matrix forms a versatile, biocompatible and nontoxic barrier for the protection of those components sensitive to the factors which are exposed to foods during processing and storage. The structure of the sodium alginate used suggests a balanced contribution of their monomers with a heterogeneous distribution block that provides greater flexibility to the gel formed. Gels of calcium alginate are formed by external gelation (GE) and internal gelation (GI) mechanism using polyvalent cations, such as Ca+2. The viscoelastic properties of the gels obtained, in general, show that an increase in [Ca+2] provides more compact gels. The differences observed between their properties indicate an influence of the source of calcium by using GI and by the gelation mechanism when the GE is used. The size distribution of the microspheres obtained by GI from different emulsions and calcium citrate indicate that the microspheres with smaller size and polydispersity occur with the polyglycerol polyricinoleate emulsifier. By encapsulating the cocoa extract rich in polyphenols in the microspheres, the experimental design shows that the amount of dispersed phase significantly affects the percentage of polyphenols retained and that the stirring speed influences the mean diameter and the polydispersity of the microspheres. Moreover, the beads obtained by extrusion are affected by increased of [Ca+2] which cause a decrease in its diameter, the morphology of these confirms an influence of the type of gelation, where the spheres obtained by GE are heterogeneous, while those formed by GI are more homogeneous. For all formulations of the spheres prepared, the beads formed by GI are presented softer and less gummy respect to those obtained by GE. The incorporation of those beads also with a high cocoa extract and [Ca+2] contents into a food product such as the gelatin shows through a sensory evaluation that the astringent and bitter flavor of the natural extract is successfully masked.

This master thesis deals with the using of microcalorimetry in the study of hydration of biopolymers. Lactose has been selected together with the other biopolymers although it is not among biopolymers but disaccharides. Selected biopolymers are alginate, dextrane, chitosan and hyaluronan of two molecular weights. Lactose has been selected for these purposes mainly because it is a model example to determine whether or not the reaction to moisture between the other samples and the saturated salt solution occurs. The biopolymer hydration study, as opposed to the commonly used perfusion calorimetry method using the possibility of measuring with adjustable moisture has been used an isothermal microcalorimetry method where at two constant temperatures the reaction of the sample to the different moisture released by the saturated salt solution was monitored.

The diploma thesis is focused on the characterisation and isolation of naturally occurred active compounds, especially on lipophilic compounds. The next part of the thesis deals with enzymes and their encapsulation into alginate particles to suggest new enzymatic dietary supplement for children with optimal nutrient composition. The theoretical part is focused on the issue of child nutrition, accordingly the necessary nutrients that children need to grow without any health difficulties. It is also focused on the availability of enzymatic food supplements for children. Finally, the theoretical part deals with the lack of chosen natural substances and their effects in connection with cancer. In the experimental part, four types of oils obtained from seeds were characterized. The oils were obtained by two methods: cold pressing with a Yoda kitchen press and extraction in an organic solvent with Soxtherm. Seeds were linseed, sesame, pumpkin, and cumin. With these oils were characterized natural active substances, polyphenols, flavonoids, antioxidants, carotenoids, chlorophylls, and fatty acids. Liposomes were also prepared from selected extracts, in which an effect on intestinal tumour cells were observed. Furthermore, some enzymes were selected, and they were encapsulated into alginate particles with average size 450 µm. In these particles was specified encapsulation efficiency as well as the proteolytic activity after testing in digest juices. The last part of this thesis was focused on the optimization of a complete enzymatic food supplement with addition of alginate particles as enzyme carriers. Samples of these supplements were finally subjected to a sensory analysis.

This diploma thesis was focused on study of barrier and transport properties of selected polyelectrolytes in hydrogel matrices by using diffusion techniques. The study of these properties was performed in horizontal diffusion cells where is observed the change in diffusion probe concentration over time. Diffusion experiments were performed on an agarose hydrogel with the addition of alginate, hyaluronic acid, polystyrene sulfonate, humic acids and as a model probe rhodamine 6G was used. Important parts of this thesis are also the methods which characterize the substances and hydrogel matrices such as rheology and potentiometric titration. The main aim of this diploma thesis was to investigate the effect of interactions between passing model dye (rhodamine 6G) and the appropriate gel (agarose + polyelectrolyte) on the fundamental diffusion parameters (effective diffusion coefficient, lag time, etc.).

Beim Tissue Engineering ist die Vaskularisierung von größeren Zell-Matrix-Konstrukten nach Implantation bis heute ein großes Problem. Durch das initiale Fehlen eines mikrovaskulären Netzwerkes kommt es zu einem raschen Zellsterben im Scaffold. Aufgrund dessen war das Ziel dieser Arbeit, im Sinne des in situ-Tissue Engineering ein Scaffold auf Basis von mineralisiertem Kollagen zu entwickeln, welches mit dem angiogenen Wachstumsfaktor VEGF funktionalisiert wird, um den Prozess der Vaskularisierung – die Einsprossung von Blutgefäßen – zu fördern und gleichzeitig durch Chemoattraktion in vivo Zellen aus dem umliegenden Knochengewebe in das Innere des Scaffolds migrieren zu lassen, so dass eine beschleunigte Defektheilung erzielt wird. Poröse Scaffolds aus mineralisiertem Kollagen wurden durch zwei unterschiedliche Strategien funktionalisiert und durch in vitro-Testungen charakterisiert. Die erste Strategie umfasste die Heparin-Modifizierung der gesamten Scaffolds, während die zweite Strategie die Injizierung eines zentralen VEGF-haltiges Depots in das Scaffoldinnere darstellte. Neben der Charakterisierung der Scaffolds wurde die Freisetzungskinetik des Modellwachstumsfaktors VEGF aus den modifizierten Scaffolds untersucht und die biologische Aktivität des freigesetzten Faktors auf Endothelzellen getestet. Zusätzlich wurde bei der 2. Strategie, der Injizierung eines Wirkstoffdepots, die Ausbildung eines Wirkstoffgradienten und die zielgerichtete Migration von Endothelzellen in Richtung des Wirkstoffdepots analysiert.

碩士
國立臺灣海洋大學
生命科學暨生物科技學系
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Heparin is the most commonly used commercial anticoagulant; however, it can potentially cause very serious side effects. Structural modification of heparin or development of heparin analogs are common methods used to reduce its side effects. These methods often involve complex synthesis procedures and expensive chemicals. Studies suggest that extracts of marine algae are rich in bioactive chemicals with many properties including anticancer, antitumor and antivirus. Sulfated algal polysaccharides, in particular, are known to have anticoagulation properties. However, extraction of such polysaccharides are time consuming and expensive, which bring about the need for chemically sulfating polysaccharides with sulfur compounds. Alginate, a non-sulfated polysaccharide, is a popular choice due to its structural similarity to heparin and low cost. Unfortunately, its low bio-stability and less than satisfactory anticoagulation efficiency limits its application. In this research, we hope to improve the anticoagulation efficiency of alginate by nanonizing its structure and sulfating its functional groups. We successfully synthesized sulfated alginate carbon nanowires (CNWsAlg@SOx) by heat treatment of alginate with ammonium sulfate at 165 °C. We have demonstrated that the CNWsAlg@SOx can inhibit thrombin activity through electrostatic interaction. Thrombin clotting time (TCT) assay revealed our CNWsAlg@SOx has 100-fold longer TCT compared to its precursor. Its low hemolytic activity demonstrated its potential for intravenous administration. Tail bleeding assay revealed that our material is 6-fold more efficient in vivo compared to its alginate precursor. We will extend our research to synthesize carbon nanomaterials by varying the carbon source and sulfur compounds to develop more efficient anticoagulants.

Beim Tissue Engineering ist die Vaskularisierung von größeren Zell-Matrix-Konstrukten nach Implantation bis heute ein großes Problem. Durch das initiale Fehlen eines mikrovaskulären Netzwerkes kommt es zu einem raschen Zellsterben im Scaffold. Aufgrund dessen war das Ziel dieser Arbeit, im Sinne des in situ-Tissue Engineering ein Scaffold auf Basis von mineralisiertem Kollagen zu entwickeln, welches mit dem angiogenen Wachstumsfaktor VEGF funktionalisiert wird, um den Prozess der Vaskularisierung – die Einsprossung von Blutgefäßen – zu fördern und gleichzeitig durch Chemoattraktion in vivo Zellen aus dem umliegenden Knochengewebe in das Innere des Scaffolds migrieren zu lassen, so dass eine beschleunigte Defektheilung erzielt wird. Poröse Scaffolds aus mineralisiertem Kollagen wurden durch zwei unterschiedliche Strategien funktionalisiert und durch in vitro-Testungen charakterisiert. Die erste Strategie umfasste die Heparin-Modifizierung der gesamten Scaffolds, während die zweite Strategie die Injizierung eines zentralen VEGF-haltiges Depots in das Scaffoldinnere darstellte. Neben der Charakterisierung der Scaffolds wurde die Freisetzungskinetik des Modellwachstumsfaktors VEGF aus den modifizierten Scaffolds untersucht und die biologische Aktivität des freigesetzten Faktors auf Endothelzellen getestet. Zusätzlich wurde bei der 2. Strategie, der Injizierung eines Wirkstoffdepots, die Ausbildung eines Wirkstoffgradienten und die zielgerichtete Migration von Endothelzellen in Richtung des Wirkstoffdepots analysiert.