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Knight, Paul Edward. "Evaluation of binding agents for the preparation of spherical granules by extrusion/spheronisation." Thesis, University College London (University of London), 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.266631.
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Qutachi, Omar. "A three domensional model for osteogenesis using controlled released simvastatin loaded polylactide-co-glycolide microparticles within embryoid bodies." Thesis, University of Nottingham, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.582000.
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To some extent formation of embryoid bodies (EBs) from embryonic stem cells (ES) mimics the events during embryonal development and can be a useful model for studying lineage commitment. However, due to morphological and structural features, the effects of direct supplementation of a molecule of interest (MOl) on EBs in cell culture to study differentiation are often limited to the superficial layers. The use of biodegradable microparticles (MPs) to deliver the MOl directly within EBs might be a promising approach for controlling ES differentiation. This study aimed to develop a 3-D model combining cells and MPs loaded with osteo-inductive molecules including simvastatin and BMP2 for ES cell-derived osteogenesis within an EB model. The steps towards achieving this aim involved; i) establishing a reliable approach for producing human and / or mouse ES cell derived EBs; ii) evaluating the osteo-inductive potential for simvastatin iii) establishing a 3-D construct of ES cell derived EBs containing simvastatin loaded MPs followed by evaluation for osteogenesis through studying different markers during formation of /osteoblast- like cells/ bone-like tissue. It was found that mouse and human ES cells could readily form EBs in a controllable manner. Simvastatin pro and! or active drug were found to induce osteogenesis of ES cells in a 2-D environment over a concentration range of 0.1 and 1 ~M. A controlled simvastin release model from MPs loaded with either the prodrug or active drug was fabricated using an emulsion method. The MPs with average diameter of 12-13 urn were designed to be distributed within EBs and provide release of the MOl over a period of three weeks. A reliable method for creating 3-D constructs of ES cell derived EBs containing MPs was tested under static or with centrifugation as well as mass suspension with avidin coated- lyophilised MPs. In this study, improved incorporation of MPs within hES cells derived EBs has been presented by coating MPs with hES cell lysate before EB formation by ~ •.......................-- centrifugation method. EBs containing MPs loaded with osteo-inductive molecules (simvastatin prodrug, active drug or BMP-2) provided a robust and reproducible 3D model for osteogenesis and the lineage commitment of HUES- 7 cells into bone cells. Results were confirmed by positive expression of major osteogenic markers at the gene level (Runx-2, Osterix and osteocalcin) and protein level (Runx-2 and osteocalcin). Extracellular matrix (ECM) formation was confirmed by Picro-sirius red staining for collagen formation and matrix mineralisation by alizarin red staining. In conclusion, the model presented in this study mimics, to some extent, the spatiotemporal presentation of locally released growth factors of early development and can be beneficial for tissue engineering purposes through achieving better presentation of the molecule of interest within the multi-cellular EB model.
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Pakalapati, Lalita Varma V. (Lalita Varma Venkata) 1976. "Controlled release microchip." Thesis, Massachusetts Institute of Technology, 2003. http://hdl.handle.net/1721.1/7976.
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Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2003.<br>Includes bibliographical references (leaf 34).<br>Microchips for constant release are not a new concept, but a controlled release chip, which does pulsatile release at variable time intervals, is clearly more efficient and useful. The process was completely understood about the theory of operation, the manufacturing procedure and the robustness of the controlled release microchip. The complete application analysis has been done along with the intellectual property study. The study involved finding out the industry opinion of the device and the usefulness of the device and all the people who might have intellectual property rights in the field. As a result numerous applications of the device have been found out along with the important parameters the device should be concentrating on have been suggested.<br>by Lalita Varma V. Pakalapati.<br>M.Eng.
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Pirone, Domenico. "Smart Controlled Release Membranes." Doctoral thesis, Universitat Rovira i Virgili, 2020. http://hdl.handle.net/10803/671550.
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L’objectiu d’aquest projecte de doctorat és millorar el rendiment dels dispositius Air Care que desenvolupen una membrana que pot alliberar les matèries primeres de perfum carregades a l’interior de l’embassament sense ser extremadament afectades per les fluctuacions de temperatura del medi extern, sent així menys significatives. sensible a la temperatura que la membrana actual usada en els productes actuals. Per fer-ho, la membrana principal es recobrirà amb un polímer modificat amb nous fragments d’azobenzen. Aquest sistema es pot desencadenar per la llum perquè actuï com una porta intel·ligent per a la difusió del perfum, millorant tant la selectivitat com alliberant el control de les matèries primeres de perfum a l’entorn de la llar / cotxe. A més, mitjançant un disseny adequat de la unitat funcionalitzadora, la temperatura podria actuar com a estímul extern addicional, capaç de desencadenar convenientment (és a dir, reduir) la permeabilitat de la membrana mitjançant una isomerització tèrmica posterior.<br>El objetivo de este proyecto de doctorado es mejorar el rendimiento de los dispositivos Air Care que desarrollan una membrana que puede liberar las materias primas de perfume cargadas dentro del depósito sin verse extremadamente afectadas por las fluctuaciones de temperatura del ambiente externo, por lo tanto, ser significativamente menos sensible a la temperatura que la membrana actual utilizada en los productos actuales. Para hacer esto, la membrana principal se recubrirá con un polímero modificado con nuevos restos de azobenceno. La luz podría activar este sistema para que actúe como una puerta inteligente para la difusión del perfume, mejorando tanto la selectividad como liberando el control de las materias primas del perfume en el entorno del hogar / automóvil. Además, mediante un diseño adecuado de la unidad funcionalizadora, la temperatura podría actuar como un estímulo externo adicional, capaz de disparar convenientemente (es decir, reducir) la permeabilidad de la membrana a través de la isomerización térmica.<br>The objective of this PhD project is to improve the performance of Air Care devices developing a membrane that can release the perfume raw materials charged inside the reservoir without being extremely affected by temperature fluctuations of the external environment, thus, being significantly less temperature sensitive than the current membrane used in nowadays products. In order to do this the main membrane will be coated with a polymer modified with novel azobenzene moieties. This system could be triggered by light to act as an intelligent gate for the perfume diffusion, improving both selectivity and releasing control of the perfume raw materials in the home/car environment. In addition, by a proper design of the functionalizing unit, temperature could act as an additional external stimulus, able to conveniently trigger (i.e. reduce) membrane permeability through thermal back-isomerization.
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Stockwell, A. F. "Oral controlled release formulations." Thesis, University of Nottingham, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.355630.
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Santini, John Thomas 1972. "A controlled release microchip." Thesis, Massachusetts Institute of Technology, 1999. http://hdl.handle.net/1721.1/8742.
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Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1999.<br>"September 1999."<br>Includes bibliographical references.<br>It is well known that the method by which a drug is delivered can have a significant effect on the drug's therapeutic efficacy. There exist numerous cases where constant release is not the optimal method of drug delivery; instead, delivery of pulses of drug at variable time intervals is the preferred method. This method is commonly referred to as pulsatile delivery, and it is preferred in some cases because it closely mimics the way in which the human body naturally produces the compounds. The objectives of this thesis were to design, fabricate, and characterize a microchip capable of achieving both pulsatile and continuous release of multiple chemical substances on demand. Each prototype microchip consisted of an array of reservoirs etched into and extending through a silicon wafer. Each reservoir was covered on one end by a thin conductive membrane that served as the anode in an electrochemical reaction. The reservoir was filled with chemicals through the other side of the reservoir and was then sealed. The proposed release mechanism had no moving parts and was based on the electrochemical dissolution of a thin anode membrane covering each reservoir. Each reservoir was independently addressable, and the electric potential was applied to an anode membrane using wires and a potentiostat. Future integration of microelectronic components may allow reservoirs to be opened on demand by a preprogrammed microprocessor, remote control, or by biosensors and biofeedback controllers. Potential advantages of the microchip for the release of drugs and other chemicals may include its small size, low power consumption, and the absence of moving parts. Such microchips may find application in a wide array of fields such as drug delivery, medical diagnostics, chemical detection. industrial process monitoring and control, and micro-scale chemical synthesis. A process was developed for producing prototype microchips using microfabrication methods such as ultraviolet photolithography, chemical vapor deposition (CYD), reactive ion etching (RTE), and electron beam evaporation. An important component of this process was a procedure for making thin ( I 000-3000 [angstroms]), unsupported, metal membrane anodes on silicon. In addition, the fabrication process was designed so that the chemicals to be released would !lever be exposed to solvents, acids, bases, or high temperatures. This was accomplished by completing all device fabrication steps before reservoir filling. This important process feature would be especially useful when dealing with easily denatured molecules such as proteins or DNA. Gold was selected as the model membrane and electrode material for the prototype controlled release microchips primarily due to its unique electrochemical properties. It is easily deposited and patterned, has a low reactivity with other substances, and resists spontaneous corrosion in most aqueous solutions over the entire pH range. However, the presence of a small amount of chloride ion in solution creates an electric potential/pH region that thermodynamically favors the dissolution of gold as water soluble gold chloride complexes. Experiments showed that gold thin films are rapidly corroded in saline solution and that corrosion occurs preferentially in the grain boundaries. Release studies were conducted to demonstrate that single and multiple substances could be released from microchip devices on demand. Sodium fluorescein (a fluorescent dye) and radioactive calcium (in the form, 45CaCI) were chosen as model substances for release due to their simplicity of detection in solution. Prototype devices were filled with one or both substances, sealed, and submerged in either phosphate buffered saline or 0.145 M NaCl solution. A potential of+ 1.04 volts relative to a saturated calomel reference electrode (SCE) was applied between a gold membrane anode covering a filled reservoir and a cathode. Electrochemical dissolution of the gold membrane anode typically occurred within 10-20 seconds of application of the potential. Once the reservoir was opened, the compound in the reservoir was able to diffuse into the surrounding solution and was detected by fluorescence spectroscopy or scintillation counting. This process was repeated to obtain multiple releases from a single device. Disintegration refers to the "falling apart" of a gold membrane over a reservoir resulting from gold corrosion and possibly. applied physical stresses. The visualization of the membrane disintegration process was achieved by videotaping the corrosion of gold membranes through a microscope. The observations from these in situ membrane disintegration experiments were then combined with gold corrosion concepts and data to develop a qualitative mechanism for the disintegration of thin. gold membranes covering chemical reservoirs. Future work should focus on materials science issues, microelectronics fabrication and packaging, and in vivo studies.<br>by John Thomas Santini, Jr.<br>Ph.D.
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Learoyd, Tristan P. "Controlled release in inhalation." Thesis, Aston University, 2007. http://publications.aston.ac.uk/11061/.
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Inhalation has become an increasingly viable alternate route to oral dosing, with the advantage of treating local disease with minimal systemic side effects (Hickey, 1992). However, increasingly complicated medication regimens associated with the necessity of the repeated dosing of multiple agents used in treating pulmonary disease has been shown to compromise both disease management and patient convenience. In this study the viability of spray drying to introduce controlled release vectors into dry powders for inhalation was investigated. The first experimental section highlights the use of leucine in producing highly respirable spray dried powders, with in vitro respirable fractions (Fine particle fraction, FPF: F < 5µm) exceeding 80% of the total dose. The second experimental chapter introduces the biocompatible polymer chitosan (mw 190 – 310 kDa) to formulations containing leucine with findings of increased FPF with increasing leucine concentration (up to 82%) and the prolonged release of the active markers terbulataline sulfate (up to 2 hours) and beclometasone dipropionate (BDP: up to 12 hours) with increasing chitosan molecular weight. Next, the thesis details the use of a double emulsion format in delivering the active markers salbutamol sulfate and BDP at differing rates; using the polymers poly-lactide co-glycolide (PLGA 50:50 and PLGA 75:25) and/or chitosan incorporating leucine as an aerosolisation enhancer the duration of in vitro release of both agents reaching 19 days with FPF exceeding 60%. The final experimental chapter involves dual aqueous and organic closed loop spray drying to create controlled release dry powders for inhalation with in vitro sustained release exceeding 28 days and FPF surpassing 55% of total loaded dose. In conclusion, potentially highly respirable sustained release dry powders for inhalation have been produced by this research using the polymers chitosan and/or PLGA as drug release modifiers and leucine as an aerosolisation enhancer.
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Hussey, Jeremy Steven. "Wood in controlled release technology." Thesis, Bangor University, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263193.
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Feely, L. C. "Controlled release hydroxypropylmethylcellulose mini-matrices." Thesis, University of Nottingham, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.373348.
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Holland, Simon J. "Novel polymeric controlled release systems." Thesis, Aston University, 1986. http://publications.aston.ac.uk/14511/.
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Fahier, Julie. "Polymeric controlled release film coatings." Thesis, Lille 2, 2016. http://www.theses.fr/2016LIL2S025/document.
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Les mini-granules enrobées offrent un grand potentiel pour la libération contrôlée de médicament par voie orale. Cependant, les mécanismes de libération impliqués ne sont pas toujours élucidés et compris. Ainsi, l’impact de certains paramètres de formulation peut être surprenant. Par exemple, il a été démontré dans ce travail :- La libération du propranolol HCl à partir de mini-granules enrobées avec du Kollicoat SR est plus lente si les mini-granules sont composées de noyaux de sucre comparé à des noyaux de cellulose microcristalline (CMC).Généralement, la tendance inverse est observée, car les noyaux de sucre ont une activité osmotique attirant plus rapidement l’eau à l’intérieur du système et entrainant ainsi, une dissolution et diffusion de la substance active. Ce résultat inattendu est dû à une association de 2 phénomènes : (i) l’effet plastifiant dû au sucre sur le film de Kollicoat SR et (ii) la diminution de la solubilité de cette SA dans le milieu de dissolution en présence de sucre dissous.De plus, le Kollicoat SR 30 D [dispersion aqueuse de poly(vinyl pyrrolidone)] offre des possibilités intéressantes de formulation par sa haute flexibilité et ses propriétés mécaniques stables. En revanche, les mini-granules composées de noyaux de sucre ont tendance à gonfler de par le cumul de l’activité osmotique du noyau et de la SA jusqu’à l’apparition de « cracks », révélés par des images obtenues par micro tomographie à rayons X.- Lorsqu’on augmente la quantité en propranolol HCl dans le système, la cinétique de libération est augmentée, particulièrement avec les mini-granules composées de noyaux de CMC.L’opposé est souvent constaté car accroitre la quantité de SA nécessite un plus grand apport en eau afin de pouvoir tout dissoudre. Les mini-granules à base de CMC présentent probablement des « cracks » malgré un faible gonflement du système, et sont accentués par l’augmentation de la concentration en propranolol HCl.En conclusion, des nouvelles connaissances sur les mécanismes de libération à partir de mini-granules enrobées avec du Kollicoat SR ont été apportées et l’importance du type de SA et la nature du noyau composant le système ont été élucidées.- Dans une deuxième partie, des mini-granules enrobées avec un mélange de polymère (Aquacoat ECD et Eudragit NM 30 D) ont été formulées dans le but de libérer la diprophylline, SA modèle, par diffusion à travers le film de polymère et de pouvoir modéliser sa cinétique à partir de modèles mathématiques<br>Polymer coated pellets offer a great potential for control drug delivery system. Nevertheless, the underlying drug release mechanisms can be complex and are not fully understood. Thus, the impact of formulation parameters can be surprising. For example, it has been demonstrated during this thesis that:- The release of propranolol HCl was slower from sugar-based pellets coated with Kollicoat SR compared to microcrystalline cellulose (MCC)-based pellets.Generally, the opposite was observed because the sugar cores are osmotically active attracting more and more water into the system leading to a fast dissolution and diffusion of the drug, especially with high water-soluble drug. This unexpected result is due to a combination of two phenomena: (i) The plasticizing effect of sugar for the film coating and (ii) Decrease in drug solubility in the release medium due to the presence of co-dissolved sugar.In addition, Kollicoat SR 30 D [an aqueous dispersion of poly(vinyl acetate) also containing small amounts of poly(vinyl pyrrolidone) and sodium lauryl sulfate] is a very interesting polymer owing to its high flexibility and stable mechanical properties. However, sugar-based pellets tend to swell by the osmotic pressure created by the high water-soluble API and the sugar until crack formation, clearly visible on the images obtained by X-ray micro tomography.- Propranolol HCl release in phosphate buffer pH 7.4 increases by increasing the drug loading into the system, especially from MCC-based pellets.The opposite was often observed since the amount of water within the drug reservoir might not be sufficient to dissolve all drug. MCC-based pellets likely presented also cracks despite a low swelling of the system, accentuated by the increase of propranolol HCl concentration.To conclude, new insights on the underlying drug release mechanisms from Kollicoat SR coated pellets were provided. The importance of the type of drug and the nature of starter cores were elucidated.- In the second part, diprophylline loaded pellets coated with a polymer blend composed of Aquacoat ECD and Eudragit NM were prepared in order to control the drug release only by diffusion through the intact polymeric film and to predict the drug kinetics using mathematical models
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Sinha, Piyush M. "Nanoengineered implantable devices for controlled drug delivery." The Ohio State University, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=osu1115138930.
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Nadkarni, Sreekant Raghuveer. "Controlled delivery of pilocarpine." Diss., The University of Arizona, 1990. http://www.gbv.de/dms/bs/toc/128390700.pdf.
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Pygall, Samuel R. "Critical processes in drug release from HPMC controlled release matrices." Thesis, University of Nottingham, 2009. http://eprints.nottingham.ac.uk/14128/.
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This study has investigated the drug release mechanisms from hydroxypropyl methylcellulose (HPMC) hydrophilic matrices. A hypothesis was developed from interpretation of a previous study that drug surface activity has an influence on drug liberation. The validity of the hypothesis was tested by studying the interactions between HPMC and the two non-steroidal anti-inflammatory drugs diclofenac Na and meclofenamate Na, using tensiometry, rheology, NMR, neutron scattering and turbimetry. Meclofenamate Na was found to interact with HPMC, resulting in detectable changes in drug diffusion coefficients and polymer structure in solution. There were increases in HPMC solution solubility and changes in viscoelasticity, which suggested drug solubilisation of the methoxyl-rich regions of the polymer chains. Diclofenac Na did not show evidence of an interaction and exhibited changes consistent with a 'salting out' of the polymer. A confocal microscopy technique was used to image the drug effects on early gel layer development. The presence of drugs affected gel layer development, depending on the level of drug in the matrix and the concentration of sodium chloride in the hydration medium. Diclofenac Na matrices became increasingly susceptible to disintegration, while meclofenamate Na matrices exhibited resistance to the effects of sodium chloride. The influence of incorporated diluents on the gel layer was also investigated and it was found that lactose had a disruptive effect, whereas microcrystalline cellulose was relatively benign. When co-formulating drugs and diluents in the matrix, lactose acted to antagonise the effect of meclofenamate, but acted synergistically with diclofenac to reduce gel layer integrity and accelerate matrix disintegration. In contrast, MCC was found to have a relatively neutral effect on drug-mediated effects. HPMC particle swelling and coalescence are critical processes in gel layer formation extending drug release. Drug surface activity and capability of interacting with HPMC appears to influence particle swelling processes, affecting gel layer formation and provides a mechanistic explanation for the differing release profiles of diclofenac and meclofenamate Na.
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Chan, Cheuk-ming. "Controlled protein release from collagen matrix." Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/HKUTO/record/B3955868X.
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Chan, Cheuk-ming, and 陳卓銘. "Controlled protein release from collagen matrix." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B3955868X.
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Gilligan, Claire A. "Controlled release polymeric films and pellets." Thesis, Queen's University Belfast, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.336028.
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Wong, Lai Pun. "Controlled-release matrices for oral administration." Thesis, Queen's University Belfast, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.336033.
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Sheldon, Jonathon. "Light Controlled Drug Activation and Release." VCU Scholars Compass, 2015. http://scholarscompass.vcu.edu/etd/4055.
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Cancer constitutes a terrible burden on modern society. In the United States there are an estimated 1,658,370 new cancer diagnoses resulting in 589,430 deaths in 2015 alone.[1] An estimated 41,170 of these cases will be diagnosed right here in Virginia. With new cancer patients comes the expanding demand for new treatments. As we all know, many modern chemotherapeutics cause adverse reactions to patients. This is because the toxic nature of these therapies often affects normal tissue alongside the tumors that are infesting the body. Therefore, researching novel ways to make chemotherapeutics selective for cancer, while leaving healthy tissue unscathed, is of paramount importance. There are a few ways in which we have approached cancer-specific chemotherapeutics. Through the use of light controlled toxicity and drug release and the targeting of tumor phenotypes such as overexpressed proteins and the Warburg effect, we begin to tackle the problem of non-specificity of current chemotherapeutics.
Combretastatin A-4 (CA4) is highly potent anticancer drug that acts as an inhibitor of tubulin polymerization.[2, 3] The core of the CA4 structure contains a cis-stilbene, and it is known that the trans isomer is significantly less potent. We prepared an azobenzene analog of CA4 (Azo-CA4) that shows 13-35 fold enhancement in potency upon external irradiation. GI50 values in the light were in the mid nM range. Due to its ability to thermally revert to the less toxic trans form, Azo-CA4 also has the ability to automatically turn its activity off with time. Therefore, this work establishes a novel strategy for switchable potency for cancer treatment.
Doxorubicin (Adriamycin) is an anthracycline type of chemotherapeutic that intercalates double-stranded DNA.[4] Although this drug has played a huge role in the treatment of cancer, its usefulness declines in cases of cancer recurrence because of the impact this drug has on the cardiovascular system. Therefore, we prepared this drug as a cell impermeable conjugate that gains penetrability through the use of external radiation.[5]
Folate receptor alpha (FRα) is overexpressed in a variety of cancer cells and accepts folic acid as a natural ligand.[6] Therefore, conjugation of drugs to folic acid introduces a promising way to bring these drugs to cancer cells with greater specificity. We took this concept one step further with the introduction of a photo-labile linker, connecting doxorubicin to folic acid, which offers dual-specificity through ligand targeting and light activation.
Finally, many cancer cells produce adenosine triphosphate, the energy currency of a cell, through an abnormal upregulation of glycolysis.[7] This pathway results in a larger-than-normal production of lactic acid and lowers the pH of cancer cells through a phenomenon known as the Warburg Effect. We hypothesized that through the use of L-canavanine, an L-arginine analog, we could construct short peptides that would gain cell permeability in a low pH environment. Attaching a cargo to these peptides, such as doxorubicin will ultimately allow for targeting the low pH extracellular environment of cancer cells. Through the use of these strategies we have furthered the fight against cancer. Targeting cancer by taking advantage of its phenotypes or through the use of light is vital in reducing negative side-effects of current chemotherapeutics. The novel technologies offered above bring us a step closer to side-effect free treatment of cancer patients.
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Bonnet, Marie. "Libération contrôlée du magnésium par des émulsions doubles : impact des paramètres de formulation." Thesis, Bordeaux 1, 2008. http://www.theses.fr/2008BOR13669/document.
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Les émulsions doubles de type eau-dans-huile-dans-eau (E/H/E) sont des systèmes dans lesquels des globules gras sont dispersés dans une phase continue aqueuse. De par leur structure compartimentée, ces systèmes permettent d’encapsuler des composés hydrosolubles au niveau des gouttelettes aqueuses internes. Néanmoins, leur utilisation requiert la maîtrise de leur stabilité thermodynamique et la compréhension des mécanismes mis en jeu au cours de la libération des espèces encapsulées. C’est dans ce contexte que différents paramètres de formulation, i.e., nature de l’huile, concentration en émulsifiant hydrophile, fraction volumique en globules gras, complexation de l’espèce encapsulée ont été testés de manière à appréhender leur influence sur la libération des ions magnésium. Les constituants utilisés pour la préparation des émulsions E/H/E sont de grade alimentaire en vue de leur application dans les secteurs pharmaceutique ou alimentaire. La fuite des ions magnésium s’effectue essentiellement par un mécanisme de diffusion/perméation. Un modèle basé sur la diffusion du magnésium à travers la phase huileuse a été proposé, prenant en compte le coefficient de perméation de l’espèce ionique, la chélation du magnésium et l’ajustement des pressions osmotiques entre les phases interne et externe. Ainsi, le coefficient de permétation dépend de la localisation et de la concentration du chélatant, mais n’est que faiblement influencé par la pression osmotique. De plus, ce coefficient évolue au cours du temps notamment pour les fractions volumiques en globules gras élevés<br>Double water-in-oil-in-water (W/O/W) emulsions are systems in which fat globules are dispersed in an aqueous continuous phase. They provide a compartmented structure that allows the encapsulation of hydrosoluble compounds in the internal aqueous droplets. Nevertheless, the application of multiple emulsions is limited by their thermodynamical instability and the possible diffusion of hydrosoluble matter from one aqueous phase to the other one through the oil layer. In this context, the influence of several formulation parameters (oil nature, hydrophilic emulsifier concentration, oil globule mass fraction, complexation of the encapsulated species) was investigated relatively to magnesium release. All the ingredients used were food grade to match pharmaceutical and food application requirements. Magnesium leakage occurred without film rupturing. A model based on diffusion was proposed in which the rate of release was determined by the permeation coefficient of magnesium across the oil phase, by magnesium chelation and by the osmotic pressure mismatch between the internal and external aqueous phases. The permeation coefficient depended on the chelating agent location and concentration but was poorly influenced by the osmotic pressure. Moreover, the permeation coefficient evolved with time, especially at high oil globule fractions
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Foster, Beth Mary. "Amphiphilic polymers for controlled release : synthesis, solution properties and release characteristics." Thesis, University of Bristol, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.549685.
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Amphiphilic polymers have long been known to display associative effects which can be exploited in controlled release applications. In particular, controlled drug delivery can benefit from the biocompatible nature of many polymers, as well as evidence of membrane affinity. This thesis describes the study of a series of amphiphilic polymers with potential for use in pharmaceutical applications. The work has ranged from development of new polymer structures with physical characteristics which may aid controlled release, through studies of polymer-drug association and disassociation in solution, to development of controlled release formulations incorporating the polymers. Novel polymers combining the controlled release potential of Pluronic triblock copolymers with that of cyclodextrins have been synthesised, via "Click Chemistry". The specificity and strong driving force behind this mechanism ensure that the molecules react covalently, to leave the cyclodextrin cavity free for complexation and controlled release of guest molecules. Commercial (unmodified) Pluronics have also been studied with drug molecules in solution, using small-angle neutron scattering and pulsed-field gradient NMR. Ibuprofen has been found to act as a cosurfactant for the Pluronic, causing an increase in aggregation but a decrease in the critical micelle concentration and temperature. Release of ibuprofen from the micelles may be triggered by an increase in solution pH, which influences the dynamic equilibrium of ibuprofen between the solution and micellar phases. Finally, new graft copolymers of polyisoprene and poly( ethylene oxide) have been found to display interesting behaviour in aqueous solution. Despite showing limited aqueous solubility, the polymers can be solubilised either by addition of other surfactant molecules, or by pre-dissolution in methanol, which is believed to enable the hydrophilic graft segments to orient outwards. The graft copolymers are capable of stabilising hydrophobic drug molecules in aqueous solution, and have also been successfully incorporated into controlled release formulations for drug delivery.
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Baawad, Abdullah. "Release of Low Acyl Gellan Gum in a Controlled Release System." University of Toledo / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1544823979777171.
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Pinardag, Fatma Esra. "Modified Acrylic Hydrogels As Controlled Release Systems." Master's thesis, METU, 2006. http://etd.lib.metu.edu.tr/upload/12607362/index.pdf.
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In this study, pH-sensitive poly(acrylamide-co-acrylic acid) hydrogels were synthesized as controlled release systems in the presence of N,N-methylene bisacrylamide as crosslinker and ammonium persulfate as initiator. A set of hydrogels were used in the form they were prepared. One set of hydrogels were prepared as porous networks by incorporating sodium chloride into the reaction medium and then leaching of it after the completion of polymerization reaction. Two sets of hydrogels were modified by argon-plasma at different discharge powers. Hydrogels were characterized by 13C-NMR, XPS, SEM, ATR-FTIR, ESR as well as equilibrium degree of swelling (EDS) and contact angle measurements. Prepared hydrogels were loaded with a model antibiotic, ciprofloxacin-HCl (CPFX), and in-vitro release of CPFX from hydrogel matrices were examined in buffer solutions of varying pH values. There are two factors determining the release rates of CPFX<br>one is the pH-dependent solubility of CPFX and the other is EDS of the hydrogel samples. For porous samples drug loading and release rates were higher when compared to the control samples and CPFX solubility dominated over release kinetics. Plasma treatment resulted in prolonged release rates in acidic medium.
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Schloßbauer, Axel. "Biofunctionalized Mesoporous Silica for Controlled Release Applications." Diss., lmu, 2010. http://nbn-resolving.de/urn:nbn:de:bvb:19-124262.
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McLellan, Bradley John. "Development of an Intraruminal Controlled-Release Device." The University of Waikato, 2007. http://hdl.handle.net/10289/2527.
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Slow-release devices retained in the rumen, are a simple method for continuous administration of bioactives to ruminant animals. To satisfy regulatory requirements and avoid waste of bioactive due to under- or over-dosing, it is advantageous to have a constant and predictable release rate. Existing intraruminal controlled-release technologies cannot easily be adapted for different bioactives or rates of release and can be influenced by the variable physiological environment in the rumen. Some existing commercial products use the pressure generated by a hydrogen gas-producing cell to extrude fluids from a syringe-like device. This technology may provide advantages for ruminal controlled-release as the gas production rate is unaffected by environment in the rumen and can be easily adjusted using electrical resistance applied to the gas cell. This technology was adapted for use in the rumen in these studies. Initial experiments identified the need for greater understanding of the rate that hydrogen is produced by the gas cell and the rate that gas diffuses through the barrel walls. Gas production rate was found to be inversely proportional to the resistance applied to the gas-producing cell. Factors affecting gas diffusion rate from the device were studied and a polymer was identified that reduced hydrogen diffusion to 5% of that for the initial components used. A relationship was developed to predict the release profile of a device. Controlled-release devices were constructed from selected materials. They released blank formulation at in vitro at a constant rate, which was within experimental variation of predicted values. Release rates from the devices used in vivo were slightly higher than predicted. The presence of rumen gases inside in vivo devices suggested that the difference may be due to inward diffusion of these gases; these may be eliminated by further study of barrel materials. Recommendations on the redesign of this technology for use as a generic intraruminal delivery system are given.
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Ambardekar, Rohan. "Controlled drug release from oriented biodegradable polymers." Thesis, University of Bradford, 2015. http://hdl.handle.net/10454/14867.
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This research is the first systematic investigation of solid-state orientation as a novel method for controlling drug release from biodegradable polymers. The effect of various degrees of polymer orientation was studied in oriented Poly (L-lactic acid) (PLA) films containing curcumin and theophylline as model drugs. Additionally, direction specific drug release was studied from oriented PLA rods containing paracetamol. The films oriented to 2X uniaxial constant width (UCW) or 2X2Y biaxial draw ratio showed retardation of drug release, when their nematic structure was stabilised by the presence of crystalline theophylline. Contrarily, the same films when contained solid solution of curcumin, shrunk in the release medium and exhibited a release profile similar to the un-oriented films. All films oriented to the UCW draw ratio ≥ 3X contained α crystalline form of PLA and showed acceleration of drug release proportionate to the draw ratio. According to the proposed mechanism augmented formation of water filled channels in these films was responsible for faster drug release. Similarly, the paracetamol loaded PLA rods die-drawn to uniaxial draw ratios ≥ 3X exhibited enhancement of drug release. Importantly, the amount of drug released along the oriented chain axis was significantly larger than that in the perpendicular direction. Drug release from the die-drawn rods was accelerated by a greater degree than that observed from the oriented films. This can be correlated to the differences in their size, geometry and the crystalline form of PLA. In conclusion, the current study provided substantial evidence that solid-state orientation can offer a control over drug release from PLA.
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Loh, Aeseun. "Controlled release of drugs from surgical suture." Thesis, Massachusetts Institute of Technology, 1987. http://hdl.handle.net/1721.1/14960.
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Thesis (B.S.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 1987.<br>MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE.<br>Bibliography: leaf 39.<br>by Aeseun Loh.<br>B.S.
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Djemai, Abdenour. "NMR studies of controlled release delivery systems." Thesis, University of Cambridge, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620473.
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Caponi, Pier Francesco. "Enzyme-responsive supramolecular assemblies for controlled release." Thesis, University of Strathclyde, 2012. http://oleg.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=18960.
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Capra, Carlo. "Controlled release of antioxidants from silica hybrids." Thesis, Loughborough University, 2005. https://dspace.lboro.ac.uk/2134/35997.
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Ternary hybrids based on poly(ethylene oxide) (PEO)/silica (SiO2)/antioxidants (AO) were produced by the sol-gel method and evaluated as slow-release antidegradants for polyamide Nylon 6. An amount of 3-glycidyloxypropyltrimethoxysilane (GOTMS) was used to compatibilise the binary combination PEO-SiO2. The antioxidants evaluated were chosen from commercial sources representing both phenolic and amine classes of molecules. In particular the antioxidants evaluated in some depth were 3,5-di-tert-butyl-4-hydroxytoluene (BHT, the lowest molecular weight hindered phenol antioxidant), octadecyl-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionate (Irganox 1076) (a higher molecular weight phenolic antioxidant), bis-(2,2,6,6-tetramethyl-4-piperidyl)-sebacate (Tinuvin 770, a sterically hindered secondary aliphatic amine stabiliser HAS), N-isopropyl-N'-phenyl-p-phenylenediamine (IPPD, an aromatic amine antioxidant).
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Podaru, George. "Exploring controlled drug release from magneto liposomes." Diss., Kansas State University, 2017. http://hdl.handle.net/2097/35544.
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Doctor of Philosophy<br>Department of Chemistry<br>Viktor Chikan<br>This thesis focuses on exploring fast and controlled drug release from several liposomal drug delivery systems including its underlying mechanics. In addition, the construction of a pulsed high-voltage rotating electromagnet is demonstrated based on a nested Helmholtz coil design. Although lots of different drug delivery mechanisms can be used, fast drug delivery is very important to utilize drug molecules that are short-lived under physiological conditions. Techniques that can release model molecules under physiological conditions could play an important role to discover the pharmacokinetics of short-lived substances in the body. In this thesis, an experimental method is developed for the fast release of the liposomes’ payload without a significant increase in (local) temperatures. This goal is achieved by using short magnetic pulses to disrupt the lipid bilayer of liposomes loaded with magnetic nanoparticles.
This thesis also demonstrates that pulsed magnetic fields can generate ultrasound from colloidal superparamagnetic nanoparticles. Generating ultrasound remotely by means of magnetic fields is an important technological development to circumvent some of the drawbacks of the traditional means of ultrasound generation techniques. In this thesis, it is demonstrated that ultrasound is generated from colloidal superparamagnetic nanoparticles when exposed to pulsed and alternating magnetic fields. Furthermore, a comparison between inhomogeneous and homogeneous magnetic fields indicates that both homogeneous and inhomogeneous magnetic fields could be important for efficient ultrasound generation; however, the latter is more important for dilute colloidal dispersion of magnetic nanoparticles. In strong magnetic fields, the ultrasound generated from the colloidal magnetic nanoparticles shows reasonable agreement with the magnetostriction effect commonly observed for bulk ferromagnetic materials. At low magnetic fields, the colloidal magnetic nanoparticle dispersion produces considerable amount of ultrasound when exposed to a.c. magnetic fields in the 20−5000 kHz frequency range. It is expected that the ultrasound generated from magnetic nanoparticles will have applications toward the acoustic induction of bioeffects in cells and manipulating the permeability of biological membranes
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Chia, Leonard Sze Onn. "Investigating controlled release pulmonary drug delivery systems." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/273209.
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The therapeutic effect of pulmonary drug delivery systems is limited by its rapid clearance from the lungs by robust clearance mechanisms. By controlling the release of drugs, the therapeutic effect of pulmonary drug delivery systems, as well as patient convenience and compliance could be improved by reducing the number of times drugs need to be administered. In this study, two controlled pulmonary drug delivery systems for drugs of different solubilities were investigated and they were characterised for their viability as effective controlled release pulmonary drug delivery systems, particularly in areas of aerosol performance and dissolution profile. A hybrid protein-polymer controlled release pulmonary drug delivery system was developed to sustain the release of a water-soluble anti-asthma drug, cromolyn sodium (CS). Two excipients with complementary characteristics – a protein, bovine serum albumin, and a polymer, polyvinyl alcohol – were formulated together with CS via co-spray drying, with varying protein-polymer ratios and drug loadings. The hybrid particles showed promise in combining the positive attributes of each excipient, with respirable particles shown to sustain the release of CS with a fine particle fraction of 30%. Combining the two excipients was complex, with further optimisation of the hybrid formulations possible. A commercially available polymer, Soluplus® was spray-dried with a poorly-water soluble corticosteroid, beclomethasone dipropionate (BDP). The resultant respirable powders were shown to have potential for use as a controlled release pulmonary drug delivery system with up to 7-fold improvement in the amount of BDP released compared to spray-dried BDP. The spray-dried BDP-Soluplus® powders were found to be amorphous, and physically stable against re-crystallisation for up to 9 months at accelerated stress test conditions with drug loadings of up to 15 % (w/w). Although it provided a platform to compare between formulations, the USP 4 flow-through cell dissolution apparatus was found to be inadequate to accurately study the dissolution profiles of the pulmonary drug delivery systems due to the formation of a gel in the apparatus. Preliminary work on the use of a novel technique to predict the crystallisation of amorphous formulations with terahertz time-domain spectroscopy was also conducted. The system confirmed the re-crystallisation tendencies of several hybrid CS/BSA/PVA formulations. Modification to the experimental setup to probe the formulations at different relative humidities instead of temperatures could yield improved results.
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Amarnath, N. "Studies in controlled release of aquatic herbicides." Thesis(Ph.D.), CSIR-National Chemical Laboratory, Pune, 1987. http://dspace.ncl.res.in:8080/xmlui/handle/20.500.12252/3292.
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Arjun, Jessica. "The development and assessment of both a separate, once-daily modified release matrix formulation of metoprolol tartrate and a combination formulation with hydrochlorothiazide." Thesis, Rhodes University, 2001. http://hdl.handle.net/10962/d1003220.
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The use of controlled release dosage forms has increased significantly in recent years as they result in increased patient compliance and higher therapeutic efficiency. This research focused on the development of a once daily dosage form that could be used for the treatment of hypertension. Both a separate sustained release dosage of metoprolol tartrate and a combination dosage form that included both an immediate release hydrochlorothiazide and a sustained release metoprolol component, were developed and evaluated. A matrix tablet, consisting of an ethylcellulose ranulation of metoprolol tartrate compressed into a hydrophilic hydroxypropyl methylcellulose polymer matrix, effectively sustained metoprolol release over a 22-hour experimental period. A multiparticulate combination dosage form that consisted of six coated mini matrix tablets of metoprolol and a powder blend of hydrochlorothiazide packed into a gelatin capsule, displayed zero order release kinetics for metoprolol release over 22 hours (r2=0.9946). The release of hydrochlorothiazide was found to be comparable to that of a commercially available product tested. Differential Scanning Calorimetry was used to identify possible incompatibilities between MPTA and excipients initially, and long term stability testing was used to assess to behaviour of the dosage form. Dissolution testing of the dosage forms was performed using USP Apparatus III, which was found to be more discriminating between the batches assessed. Dissolution curves were evaluated for similarity and difference using f1 and f2 fit factors. Samples were analyzed using a high performance liquid chromatographic method that was developed and validated for the simultaneous determination of the compounds of interest. Various factors influencing drug release from the developed dosage forms were assessed and recommendations for further optimization of the formulation are made. Factors evaluated included the quantity of granulating fluid, matrix polymer content, drug load and process variables, including drying time and compression force. The influence of various coating levels on drug release was assessed and none of the levels assessed were found to adequately retarded drug release over a 22-hour period. Combinations of tablets coated to different levels allowed for the successful development of a sustained release metoprolol component, which could be included into the combination dosage form.
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Ammendola, Mario. "Solvent stable microcapsules for controlled release of actives." Doctoral thesis, Universitat Rovira i Virgili, 2020. http://hdl.handle.net/10803/670306.
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En el present treball, l'objectiu principal és el desenvolupament de microcàpsules estables amb dissolvents per a l'alliberament controlat d'actius, que s'inclouran en les aplicacions de béns de consum. El material principal s'anomena Sweet & Smart (S&S). És una barreja de fragàncies amb un alt contingut de materials amb baix logP. L’encapsulat de S&S permetria una flexibilitat més àmplia en les formulacions de perfum, aportant valor comercial als béns de consum. Un altre punt important del treball és la sostenibilitat, a causa de les tendències socials modernes.
El primer pas del treball va ser la selecció dels materials. Hem seleccionat acetat de cel·lulosa (CA) com a material de paret. CA compleix les nostres consideracions mediambientals i supera la prova de cribratge.
El segon pas va ser l’exploració de la tècnica d’encapsulació. Primerament, hem utilitzat el spray dryer per la seva facilitat i escàs cost. A continuació, vam desenvolupar un procés d’encapsulació, la separació de fase induïda pel vapor (VIPS) implementant la tècnica de precipitació d’immersió (IPS). Es va utilitzar vapor no dissolvent en lloc de líquid no solvent per induir la separació en fase de la solució polimèrica. La tercera tècnica és l'evaporació de dissolvents amb Pickering emulsifier. Los Pickering emulsifier són partícules sòlides que estabilitzen una emulsió en lloc de tensioactius.
Les microcàpsules es van caracteritzar mitjançant diferents tècniques. La morfologia de les microcàpsules és un punt crucial. Una estructura core-shell permet optimitzar la quantitat de perfum que contenen les càpsules i el seu alliberament. Per tant, l’activitat de les càpsules i l’eficiència d’encapsulat prenen un valor molt important.
Finalment, es va avaluar el rendiment de les microcàpsules en un test industrial estàndard per avaluar la seva possible aplicació en formulacions completes de producte.<br>La tesis se centra en la producción y caracterización de microcápsulas poliméricas. Las microcápsulas están constituidas por una cubierta polimérica que contiene un material central atrapado en su interior. Los motivos de la encapsulación son la protección y el control de la liberación del activo.
En el presente trabajo, el objetivo principal es el desarrollo de microcápsulas solventes estables para la liberación controlada de activos, que se incluirán en las aplicaciones de bienes de consumo. El material principal se llama Sweet & Smart (S&S). Es una mezcla de fragancias con un alto contenido de materiales de bajo logP. La encapsulación de S&S permitiría una mayor flexibilidad en las formulaciones de perfumes, aportando valor comercial a los bienes de consumo. Otro punto importante del trabajo es la sostenibilidad, debido a las tendencias sociales modernas.
El primer paso del trabajo fue la selección de los materiales. Seleccionamos acetato de celulosa (CA) como material de pared. CA cumple con nuestras consideraciones ambientales y pasó la prueba de detección.
El segundo paso fue la exploración de la técnica de encapsulación. En primer lugar, utilizamos el secado por pulverización debido a su facilidad y bajo costo. Luego, desarrollamos un proceso de encapsulación, la separación de fases inducida por vapor (VIPS) mediante la implementación de la técnica de precipitación por inmersión (IPS). Utilizamos vapor no solvente en lugar de líquido no solvente para inducir la separación de fases de la solución polimérica. La tercera técnica es una evaporación de solvente usando una Pickering emulsion. Los Pickering emulsifier son partículas sólidas que estabilizan una emulsión en lugar de tensioactivos.
Las microcápsulas se caracterizaron mediante diferentes técnicas. La morfología de las microcápsulas es un punto crucial. Una estructura core-shell permite optimizar la cantidad de perfume contenido en las cápsulas y su liberación. Por lo tanto, la actividad de las cápsulas y la eficiencia de encapsulación adquieren un valor muy importante.
Finalmente, se evaluó el rendimiento de las microcápsulas en una prueba industrial estándar para evaluar su aplicación potencial en formulaciones completas de productos.
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Uylukcuoglu, Beyza. "Chitosan Microspheres And Films Used In Controlled Release." Master's thesis, METU, 2003. http://etd.lib.metu.edu.tr/upload/2/1252659/index.pdf.
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Thalassemia, a genetic blood disorder, occurs as a result of deformations of hemoglobin structures. Patients with thalassemia develop iron overload from chronic blood transfusions and require regular iron chelation to prevent potentially fatal iron-related complications. Deferiprone is a commercially available drug used as iron chelator for the treatment of thalassemia but the very long-term effectiveness is not clearly known yet. Therefore, some studies were carried out to find effective alternative drugs or delivery methods for treatment of thalassemia. Controlled delivery, which offers safer, more convenient, and more effective means of administering actives, seems promising with this respect. Chitosan, a natural biopolymer produced from deacetylation of chitin, has a variety of promising pharmaceutical uses and is presently considered as a novel carrier material in drug delivery systems.
In this study, chitosan microspheres having different degree of deacetylation (DDA) and containing Deferiprone were prepared by oil/water emulsion method and by crosslinking with gluteraldehyde. Particle size, SEM, and in vitro drug release analysis were performed. The average sizes of the prepared microspheres increased with increasing degree of deacetylation of chitosan and with decreasing crosslinking degree. In vitro drug release studies showed that, the release rate of Deferiprone increased as the crosslinking degree increased, contrary to the expectations. This is explained by the crystalline structure of lightly crosslinked chitosan which have ordered and dense structure causing slower release rate for Deferiprone compare to highly crosslinked structures.
In the second stage of the study, chitosan films hardened with gluteraldehyde were prepared by film casting method. IR, DSC and mechanical analysis were performed. For the films with various crosslinking degrees, it was found that UTS values differed from 50.6 MPa to 102.7 MPa, mean elastic modulus values differed from 3328.7 MPa to 3790.1 MPa and SAB values differed from 2.06% to 4.29%.
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Paulsson, Mattias. "Controlled Release Gel Formulations for Mucosal Drug Delivery." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2001. http://publications.uu.se/theses/91-554-5173-X/.
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Ng, Anna. "Taste-masked and controlled-release formulations of chloroquine." Thesis, University College London (University of London), 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.267929.
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Loxley, Andrew L. "Polymer microcapsules with liquid cores for controlled release." Thesis, University of Bristol, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.265360.
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Hyde, Thomas Miles. "Transport in polymers : application to controlled drug release." Thesis, University of Cambridge, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.363822.
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Kanga, Yao. "Controlled release of Isothiazoline biocides from industrial minerals." Thesis, University of Birmingham, 2011. http://etheses.bham.ac.uk//id/eprint/1594/.
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This project investigated how various minerals of different surface areas and morphologies can be used to adsorb isothiazoline biocides for controlled-release and antimicrobial purposes. The absorption of the biocides on the mineral powders was achieved by way of using a bench high shear mill (dry process), or combining them to hydrated minerals (wet process). The characterisation of the minerals was achieved by XRF (chemical composition), XRD (crystal composition), SEM (morphology), B.E.T nitrogen (surface area), and Light Scattering (particle size distribution). HPLC was used to determine the concentration of the biocide in solution, and the Flow Microcalorimeter used to measure the bond strength between the biocide molecules and the minerals. The minerals were added to an exterior paint made according to an Imerys in-house formulation. Various modifications of this initial coating formulation were made in order to compare the biocide 2-Octyl-4-isothiazolin-3-one (OIT) release profiles from impregnated and non-impregnated minerals. Montmorillonite clay was the best performing mineral in all experiments (adsorption and desorption both from the minerals and paints films, strength of bond analysis, and bioassay). All other minerals tested carried the biocide with varying degree of success. Optical and mechanical tests performed on paint films containing various minerals suggested there were no significant differences between the films. Rheology tests demonstrated that newly developed formulations were easy to apply to a surface.
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Wang, Yana Ph D. Massachusetts Institute of Technology. "Engineering chemoattractant gradients using controlled release polysaccharide microspheres." Thesis, Massachusetts Institute of Technology, 2011. http://hdl.handle.net/1721.1/70407.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, February 2012.<br>Cataloged from PDF version of thesis.<br>Includes bibliographical references (p. 111-122).<br>Chemoattractant gradients play important roles in the normal function of immune system, from lymphocyte homeostasis to mounting efficient immune responses against infection. Improved fundamental knowledge about the role of chemoattractant gradients developed around single source cells in controlling chemotaxis of "receiving" cells would not only greatly advance our understanding of the basic mechanisms of cell chemotaxis but also would inform strategies for modulating chemoattractant gradients in therapeutic applications, such as adjuvant materials for vaccines and cancer immunotherapy recruiting immune cells of interest. In this thesis, we first applied mathematical modeling to understand the key characteristics of chemoattractant gradients secreted from single source cells at physiological rates. During the transport of chemoattractants, we considered the diffusion of soluble attractants, binding to matrix and degradation by proteolytic enzymes. From the calculated chemoattractant concentration gradients, we predicted the characteristics of attractant receptor engagement on responding cells, and estimated the maximum stimulation distance effectively triggering chemotaxis of responding cells based on the threshold for receptor engagement gradients, a difference of ~10 ligand-engaged receptors between the front and back of responding cells. This characteristic maximum stimulation distance is a function of multiple parameters including secretion rate of the source cell, diffusion constant of the chemoattractant, interaction with matrix, degradation or clearance of chemoattractant in the tissues, and the density of source cells. In addition, chemokine receptor desensitization induced by chemoattractants could shorten the maximum stimulation distance. We then developed Artificial Secreting Cells (ASCs) to mimic real chemoattractant secreting cells using cell-sized polysaccharide-based hydrogel microspheres releasing chemoattractant in a controlled manner. These alginate hydrogel microspheres, ~30 [mu]m in size, were crosslinked with Ca2+ between gluronic acid units on alginate backbones and provided a natural and bioactive environment for chemokines. The chemokines could be loaded into these alginate microspheres by soaking them in concentrated chemokine solutions and released in a reversible manner. This approach was shown as a general strategy for several chemokines, such as CCL21, CCL19, CXCL10 and CXCL12. The loading and release properties of individual chemokines were highly correlated with the average charge density on protein surface. We have also demonstrated that the controlled gradients created by ASCs were similar to the modeled gradients developed around single source cells. Further we used 3D collagen hydrogels embedded with ASCs as an in vitro model to investigate single human T-cell and dendritic cell migration dynamics to CCL21 and CCL19 chemokine gradients. Individual T-cells exhibited a binary response to isolated attractant sources, migrating highly directionally or ignoring the gradient completely; the fraction of responding cells correlated with chemokine receptor occupancy induced by the gradient. In sustained gradients eliciting low receptor desensitization, attracted T-cells or dendritic cells swarmed around isolated ASCs for hours. With increasing ASC density, overlapping gradients and high attractant concentrations caused a transition from local swarming to transient "hopping" of cells bead to bead. Thus, diverse migration responses observed in vivo may be determined by chemoattractant source density and secretion rate, which govern receptor occupancy patterns in nearby cells.<br>by Yana Wang.<br>Ph.D.
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Mudumba, Sujata S. "Mucoadhesive controlled release ciprofloxacin nanoparticles for pulmonary delivery." Scholarly Commons, 2010. https://scholarlycommons.pacific.edu/uop_etds/2425.
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Controlled release of drugs to the lungs is an interesting and evolving field of research. The influence of physicochemical properties of nanoparticles on the controlled release of ciprofloxacin and in-vivo pharmacokinetics following pulmonary administration was evaluated. The physicochemical properties had an effect on encapsulation efficiency and surface charge, but no significant effect on particle size. The in-vitro release profiles of ciprofloxacin in phosphate buffered saline showed small differences over the range of physicochemical properties evaluated. The physicochemical properties of ciprofloxacin nanoparticles resulted in variable and unreliable nebulizer output using a vibrating mesh nebulizer whereas the impact on the aerosol properties of a jet nebulizer was negligible. Addition of mucoadhesive polymers in the nanoparticles had a three-fold increase in apparent half-life in rats by releasing ciprofloxacin over an extended release period on the surfaces of the lungs.
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Yeh, Hsi-wei. "Investigation of Polymeric Composites for Controlled Drug Release." VCU Scholars Compass, 2017. http://scholarscompass.vcu.edu/etd/4971.
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The Electrospray (ES) technique is a promising particle generation method for drug delivery due to its capabilities of producing monodisperse PLGA composite particles with unique configurations and high drug encapsulation efficiency. In the dissertation work, the coaxial dual capillary ES was used to generate drug-loaded core-shell PLGA particles to study the effects of particle filling materials, drug loading locations and particle shell thicknesses on the resultant in vitro release behaviors of the hydrophilic and/ or hydrophobic model drugs. Through release profile characterization of drug-loaded PLGA particles (particle size: 400 nm and 1 μm), it was confirmed that the co-encapsulation of Budesonide (BUD, the hydrophobic small-molecule model drug) and Theophylline (THY, the hydrophilic small-molecule model drug) in the particle cores is the most effective drug loading strategy for extended release of the fixed combined BUD and THY. Particles composed of PLGA fillers with lower molecular weights and with greater shell layer thicknesses could release THY in a well controlled fashion. On the other hand, a slower release rate of Bovine Serum Albumin (BSA, the protein model drug) from PLGA particles with greater shell thickness was also observed. Sequential release of BSA and Paclitaxel (PTX, the hydrophobic small-molecule anti-cancer model drug) was achieved by the 400-nm PLGA (Mw: 7,000-17,000 g/mol, LA/GA: 50/50) particles with potential biopharmaceutical applications in cancer therapy.
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LI, RUO. "CHITOSAN PARTICLES FOR THE CONTROLLED RELEASE OF PROTEINS." Doctoral thesis, Politecnico di Torino, 2012. http://hdl.handle.net/11583/2497932.
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Back Ground Chitosan as a natural polymer has been fabulated into a number of formulations such as films, hydrogels and particles based on its excellent properties such as biodegradable, biocompotable, bioadhesive, permeartion-enhancement, antibiotic, antitumor etc. properties. Among them, chitosan microparticles found a lot of applications in pharmaceutics such as vaccine delivery, mucosal delivery and gene delivery, etc. Down to the nanoscale, chitosan nanoparticles have more attractive properties more than that of chitosan microparticles, which further widen the applications of chitosan particles in biomedicine and biopharmaceutics.
Objective of this Thesis This thesis is aimed to prepare chitosan micro or nanoparticles to delivery proteins.
What are the questions this thesis attempted to solve? 1) What are the proper preparation conditions of chitosan micro or nanoparticles? 2) How does the pH value affect the formation and protein encapsulation of chitosan nanoparticles? 3) How to overcome the burst release of chitosan nanoparticles? 4) How to overcome the aggregation disadvantage in the contritional preparation process of TPP-gelated chitosan microparticles? 5) How to construct a composite particles system to realize the sustainable release of proteins?
What are the methods used in this thesis? 1) ionotropic gelation method to prepare chitosan nanoparticles 2) Emulsification-coacervation (NaOH) method to prepare chitosan microparticles 3) a polyelectrolytes coacervation method to prepare chitosan-BSA complexes 4) a microemulsion involved emulsification-coalescence method to prepare TPP-gelated chitosan microparticles 5) a nanoparticles encapsulation method to prepare composite particles.
Results and Conclutions 1) the effect of preparation parameters on the properties of chitosan nanoparticles: 1a) the concentration of chitosan has no siganificant effect on particles yield, positively associated with particles size, size distribution, positively associated with BSA encapsulation efficiency in a specific concentration range; 1b) the mass matio of chitosan to TPP negatively associated with particles yield, positively associated with particle size and size distribution, negatively associated with BSA encapsulation efficiency; 1c) the concentration of BSA has no significant effect on particles yield, particle size or size distribution, negatively associated with BSA encapsulation efficiency in a specific concentration range. 2) a chitosan polymer chain conformation related mechanism is proposed through the study of the effect of pH value on the formation and BSA encapsulation of chitosan nanoparticles. 3) the most homogeneous and smooth chitosan particles could be obtained at the parameters of: 2% (m/v) chitosan solution, 2/10 w/o volume ratio, 4% Span 85 as susfactant, 5 Krpm homogenization speed and 3 times addition of NaOH solution as a coacervation agent. The obtained particles have a mean diameter of 9.4±1.9 m. The BSA loading test found that dispersed particles only could be obtained below the BSA concentration of 0.5% under above mentioned parameters. 4) a noval polyelectrolytes complex formed by TPP and BSA is obtained attempted to solve the burst release effect of chitosan nanoparticles. 5) a microemulsion involved emulsification-coalescence method is used to overcome the aggregation problem of TPP-gelated chitosan microparticles. 6) a chitosan nanoparticles encapsulated PLA composite particles are successfully constructed.
What is new in this thesis? 1) to study the formation mechanism and protein encapsulation of chitosan nanoparticles through the study of the effect of pH value on their properties and propose the role of chitosan polymer chain conformation during this process, 2) a noval TPP-BSA polyelectrolytes complex is obtained base on the purpose to overcome the burst release effect of chitosan nanoparticles, 3) apply emulsification-coalescence method in which a microemulsion of cross-linking agent-TPP is used to solve the aggregation problem of TPP-gelated chitosan microparticles, 4) propose a chitosan nanoparticles encapsulated PLA composite particles to control the release of proteins.
Where is the study of this thesis in the field? 1) Chitosan nanoparticles have been extensively investigated in the past few years and the factors which can affect the properties of chitosan nanoparticles have been well documented as well. This thesis provides the evidence from a new side to understand the formation and protein encapsulation mechanisms of chitosan nanoparticles. 2) New and highly effective methods have been proposed by others to prepare protein loaded chitosan microparticles such as sieving and microfluidic methods which can reproduceably scale up the production of monodispersed chitosan microparticles. This thesis just solved a technique problem in the conventional preparation process of TPP-gelated chitosan microparticles. 3) The proposed TPP-BSA polyelectrolytes complex could be an alternative route to overcome the burst release effect of chitosan nanoparticles. 4) The proposed chitosan nanoparticles encapsulated PLA composite particles is one of the solutions among other composite particles proposed by others.
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Sinha, Piyush Mohan. "Nanoengineered implantable devices for controlled drug delivery." Connect to this title online, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1115138930.
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Tolia, Gaurav. "Use of Silicone Adhesive for Improving Oral Controlled Delivery." University of Cincinnati / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1521190743860228.
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Guse, Christian. "Triglyceride matrices for controlled release characteristics for manufacturing and release ; biocompatibility and erosion behavior /." [S.l.] : [s.n.], 2005. http://deposit.ddb.de/cgi-bin/dokserv?idn=975739263.
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