Dissertations / Theses on the topic 'Protein based delivery systems'
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Squire, Marie A. "Protein-based drug delivery systems." Thesis, University of Canterbury. Chemistry, 2004. http://hdl.handle.net/10092/6518.
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The targeted delivery of drugs is one of the most actively pursued goals in anti-HIV and anti-cancer chemotherapy. This project takes a proof-of-concept approach to the development of protein-based drug delivery systems - delivery systems that would package, target, and deliver cytotoxins to diseased cells.
Primarily, this project explores the use of the potent anti-HN protein, cyanovirin-N (CV-N), to actively target and deliver cytotoxic natural products to HN-infected cells. This project also investigates the use of human serum albumin (HSA), a 66 kDa protein, as a macromolecular carrier to passively target and deliver cytotoxic natural products to cancerous cells.
To facilitate release of the toxin within infected cells, an enzymatically-cleavable tetra peptide was incorporated in the conjugates. Maleimido-activated tetra peptide toxin constructs were prepared in readiness for selective reaction with proteins carrying thiol functionalities. Release of the toxin, norhomohalichondrin B, was demonstrated in vitro.
Native CV -N conjugates were prepared by thiolation of the lysine ε-amino groups, and the subsequent reaction with maleimido-activated compounds. Reaction across all lysine residues was demonstrated. A singly-substituted tyrosinamide conjugate of CV-N was prepared. Two recombinantly produced mutant CV-N proteins allowed for the production of selectively modified, double- and single-norhomohalichondrin B conjugates of CV-N. The conjugates retained the anti-HN activity of the parent protein.
Homohalichondrin B, doxorubicin, and tyrosinamide conjugates of HSA were prepared. The syntheses exploited the availability of a free thiolmoiety at cysteine-34 of HSA, and the specific and selective reaction of this thiol with the maleimido-activated tetra peptide derivatives.
All toxin conjugates demonstrate excellent cell toxicity. Further research to investigate whether this is targeted toxicity is currently underway.
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Jørgensen, Lene. "Lipid based drug delivery systems for parenteral delivery of proteins /." Cph. : Department of Pharmaceutics, the Danish University of Pharmaceutical Sciences, 2004. http://www.dfh.dk/phd/defences/lenejoergensen.htm.
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Konovalova, M. V., D. S. Khramova, A. V. Ilyina, and D. V. Kurek. "Polysaccharides Based Nanoparticles as Protein Oral Delivery System." Thesis, Sumy State University, 2013. http://essuir.sumdu.edu.ua/handle/123456789/35483.
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Ovalbumin loaded chitosan and pectin based composite nanoparticles were obtained. The mean size,
morphology and zeta potential of the nanoparticles were determined by dynamic light scattering (DLS) and
atomic force microscopy (AFM). Effect oral administration of obtained nanoparticles on the immune response
was studied.
When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/35483
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Schwab, Martin. "Degradation of lipid based drug delivery systems and characterization of semi-synthetic spider silk proteins for the application in pharmaceutical technology." Diss., Ludwig-Maximilians-Universität München, 2009. http://nbn-resolving.de/urn:nbn:de:bvb:19-165238.
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Schwab, Martin [Verfasser], and Gerhard [Akademischer Betreuer] Winter. "Degradation of lipid based drug delivery systems and characterization of semi-synthetic spider silk proteins for the application in pharmaceutical technology / Martin Schwab. Betreuer: Gerhard Winter." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2014. http://d-nb.info/1046785257/34.
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游, 晧欣. "Development of novel systems promoting intracellular protein delivery." 京都大学 (Kyoto University), 2012. http://hdl.handle.net/2433/157905.
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Heffernan, Michael John. "Biodegradable polymeric delivery systems for protein subunit vaccines." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2008. http://hdl.handle.net/1853/24787.
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Thesis (Ph.D.)--Biomedical Engineering, Georgia Institute of Technology, 2008.Committee Chair: Dr. Niren Murthy; Committee Member: Dr. Carson Meredith; Committee Member: Dr. Julia Babensee; Committee Member: Dr. Mark Prausnitz; Committee Member: Dr. Ravi Bellamkonda.
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Pape, Valerie Elizabeth. "Methotrexate-protein conjugates as soluble drug delivery systems." Thesis, University of Bath, 1990. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.277877.
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Liu, Weipeng. "Biopolymer-based ocular drug delivery systems." Diss., Connect to online resource - MSU authorized users, 2008.
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Estey, Tia Brie. "Protein instability associated with PLGA delivery systems and UV-induced protein oxidation /." Connect to full text via ProQuest. IP filtered, 2006.
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Thesis (Ph.D. in Pharmaceutical Sciences) -- University of Colorado, 2006.Typescript. Includes bibliographical references (leaves 144-161). Free to UCDHSC affiliates. Online version available via ProQuest Digital Dissertations;
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Tantipolphan, Ruedeeporn, and n/a. "Characterisation of protein-phospholipid interactions in implantable delivery systems." University of Otago. School of Pharmacy, 2007. http://adt.otago.ac.nz./public/adt-NZDU20071218.162425.
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Purpose: This thesis aimed to gain a better understanding of the effects of salts in modifying in vitro phase behaviour of lecithin and cholesterol solid implants and to obtain further information on in vitro protein release and stability.
Methods: Raman spectroscopy and partial least squares regression (PLSR) were used to investigate lecithin-cholesterol molecular interactions as a function of method of preparation. Lipid-salt interactions were studied by attenuated total reflectance Fourier transform infrared (ATR-FTIR) and Raman spectroscopy using principal component analysis (PCA). In vitro release of bovine serum albumin (BSA), a model protein, from lecithin and lecithin:cholesterol implants comprising 10 and 30% NaCl and CaCl₂ were performed. Size exclusion (SE) HPLC was used for quantitative and qualitative analysis of the released BSA. On hydration, changes in phase behaviour and implant morphology were studied by ATR spectroscopy and light microscopy. SE-HPLC, ATR and fluorescence spectroscopy were used to evaluate the structure of unreleased BSA. Protein adsorption on lipid films was studied by flow through ATR spectroscopy. Increased amide II peak area upon recirculation of BSA in salt solutions over hydrated lecithin and lecithin:cholesterol films cast on ZnSe prisms was used to quantify the deposition of BSA onto the lipid surfaces.
Results: Shifts in the Raman spectra suggested the lecithin headgroup may be involved in lecithin-cholesterol interactions. Greater R� and root mean square error of cross validation in the calibration curves of physical mixing and heating (120�C) methods reflected poor mixing in these preparations. The mean absolute residue and mean Mahalanobis distance values from the physical mixing and granulation methods indicated their spectral similarity and comparable level of lecithin-cholesterol interactions. Calcium exhibited stronger affinity for phospholipids than sodium and it induced headgroup hydration and reorganisation upon binding. PCA of ATR spectra was sensitive to cholesterol addition, calcium binding and method of preparation whilst PCA of Raman spectra only differentiated the presence of cholesterol. In vitro release of BSA from implants produced from wet granulation mixtures of lecithin and lecithin:cholesterol in the absence of salt showed retention of a high monomer content and the release profiles were similar to the literature. Cholesterol increased the swelling, induced phase transformation of lecithin and, subsequently, reduced the BSA release. Salts only slightly modified the BSA release from the lecithin implants. In contrast, for lecithin:cholesterol matrices salts greatly enhanced implant swelling, induced the formation of hydrated lecithin of heterogeneous size and inhibited the in vitro BSA release. Analyses of the protein showed increased aggregation of BSA with a high retention of native structure while retained within the swollen matrices. ATR spectra suggested that salts promoted protein adsorption onto hydrated lecithin surfaces and the effects depend on salt types (NaCl > CaCl₂) and concentration (0.1 M > 1.0 M) but not on lecithin:cholesterol surfaces.
Conclusion: PLSR and PCA can be used to investigate molecular interactions in the solid lipid matrices. In lecithin:cholesterol implants, salts modified the phase behaviour of lecithin which resulted in enhanced swelling, formation of hydrated lecithin of altered morphology and inhibition of in vitro BSA release.
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Mok, Kenneth W. C. "Characterization of lipid-based DNA delivery systems." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ34590.pdf.
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Senderoff, Richard I. "Development of fibrin-based drug delivery systems /." The Ohio State University, 1990. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487677267728699.
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Mawad, Damia Graduate School of Biomedical Engineering Faculty of Engineering UNSW. "Development of Novel hydrogels for protein drug delivery." Awarded by:University of New South Wales. Graduate School of Biomedical Engineering, 2005. http://handle.unsw.edu.au/1959.4/25221.
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Introduction: Embolic agents are used to block blood flow of hypervascular tumours, ultimately resulting in target tissue necrosis. However, this therapy is limited by the formation of new blood vessels within the tumour, a process known as angiogenesis. Targeting angiogenesis led to the discovery of anti-angiogenic factors, large molecular weight proteins that can block the angiogenic process. The aim of this research is development of poly (vinyl alcohol) (PVA) aqueous solutions that cross-link in situ to form a hydrogel that functions as an embolic agent for delivery of macromolecular drugs. Methods: PVA (14 kDa, 83% hydrolysed), functionalised by 7 acrylamide groups per chain, was used to prepare 10, 15, and 20wt% non-degradable hydrogels, cured by UV or redox initiation. Structural properties were characterised and the release of FITCDextran (20kDa) was quantified. Degradable networks were then prepared by attaching to PVA (83% and 98 % hydrolysed) ester linkages with an acrylate end group. The effect on degradation profiles was assessed by varying parameters such as macromer concentration, cross-linking density, polymer backbone and curing method. To further enhance the technology, radiopaque degradable PVA was synthesised, and degradation profiles were determined. Cell growth inhibition of modified PVA and degradable products were also investigated. Results: Redox initiation resulted in non-degradable PVA networks of well-controlled structural properties. Increasing the solid content from 10 to 20wt% prolonged the release time from few hours to ~ 2 days but had no effect on the percent release, with only a maximum release of 65% achieved. Ester attachment to the PVA allowed flexibility in designing networks of variable swelling behaviors and degradation times allowing ease of tailoring for specific clinical requirements. Synthesis of radiopaque degradable PVA hydrogels was successful without affecting the polymer solubility in water or its ability to polymerize by redox. This suggested that this novel hydrogel is a potential liquid embolic with enhanced X-ray visibility. Degradable products had negligible cytotoxicity. Conclusion: Novel non-degradable and radiopaque degradable PVA hydrogels cured by redox initiation were developed in this research. The developed PVA hydrogels showed characteristics in vitro that are desirable for the in vivo application as release systems for anti-angiogenic factors.
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Webster, Alexandra Margaret. "Design, synthesis and delivery of peptide-based systems." Thesis, Durham University, 2018. http://etheses.dur.ac.uk/12616/.
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Peptide-based therapeutics have been an active area of research for a number of years. They have been found applications as drug-delivery agents, anticancer therapies and as antibiotics, the latter of which is particularly notable when set against a present-day backdrop of the increasing problem of antibiotic resistance. However, the use of peptides is still limited as they suffer from poor bioavailability as a result of their vulnerability to proteolytic degradation. Peptoids are a class of peptidomimetics which represent a potential proteolytically stable alternative to peptides. Chapter 1 introduces peptoids, common methods of their synthesis and their potential therapeutic applications. The challenges associated with controlling peptoid secondary structure are also discussed, along with commonly seen methods of imposing conformational rigidity. Chapter 2 details our attempts to address this problem by synthesising a library of biaryl-containing cyclic peptoids which represent novel peptoid scaffolds. In Chapter 3, we synthesise the active domain (p15) of the known anticancer peptide CIGB-300 along with three stapled analogues on which binding assays can be carried out. In Chapter 4, we synthesise six cell-penetrating peptoids (CPPos) which have previously been reported to localise in mitochondria. Onto these peptoids we conjugated the known anticancer peptide D-KLA and show the ability of these peptoids to increase proapoptotic activity. Flow cytometry and confocal microscopy is then used to demonstrate mitochondrial localisation of the most active peptide-peptoid hybrid, KLA-CPPo6. Having shown the ability of CPPos to transport biologically active cargo, we then conjugate the p15 peptide, previously introduced in Chapter 3, to the six CPPos in preparation for the evaluation of their anticancer activity.
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Mackenzie, R. C. "Computational modelling of polymer-based drug delivery systems." Thesis, University of Nottingham, 2015. http://eprints.nottingham.ac.uk/28852/.
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Polymer-based drug delivery systems have fantastic potential in chemotherapy as they can reduce drug side effects, help in patient compliance and provide targeting. Nanoprecipitation is used to encapsulate small drug molecules into polymer nanoparticles to form a drug delivery system. A major obstacle in polymer-based drug delivery systems reaching the clinic is their inability to load sufficient drug molecules. Little is known about the processes involved in the encapsulation of drug molecules into these delivery systems. An insight into the processes that govern the formation of these particles and encapsulation of small drug molecules within them is therefore desirable. We used molecular dynamics to model nanoprecipitation by simulating the dispersion of an acetone drop, containing polymer, into water containing drug. To allow sufficient dispersion of acetone a large amount of water is required, thus coarse-graining becomes mandatory. However, we maintain accuracy for our polymer-drug interactions by using a multiscale force field. Atomistic polymer and drug molecules contain coarse-grain virtual sites which facilitate interactions with the coarse-grain solvent molecules. We also employed fully atomistic reference simulations via resolution transformation to optimise our multiscale force field. This thesis details the theory and design behind this model of nanoprecipitation including how other techniques produced inferior results. Initial simulations with our multiscale model matched an experimental trend and were shown to be accurate relative to atomistic reference simulations. We also analysed a fully atomistic simulation of nanoprecipitation that took several months to complete. This atomistic simulation was used as a reference to update the multiscale force field. The updated force field improved on some aspects of the simulation but there are still areas that need improvement. Insight from the simulations provides an understanding of the experimental results and trends. The transferability of the model should help in designing more efficient polymer-based drug delivery systems in the future. We conclude with future work on modelling polymer-based drug delivery systems including alternate methods to gain understanding of not only drug incorporation but also drug release.
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Peagram, Rebecca Elizabeth. "Emulsion formulations as delivery systems for soluble protein subunit viral vaccines." Thesis, University of Nottingham, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.363615.
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Fach, Lars Matthias [Verfasser]. "Protein-based nanoparticles for drug delivery applications / Lars Matthias Fach." Mainz : Universitätsbibliothek Mainz, 2018. http://d-nb.info/116056146X/34.
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Steiert, Elena [Verfasser]. "Dynamic Protein-based Nanoparticles for Drug Delivery Applications / Elena Steiert." Mainz : Universitätsbibliothek Mainz, 2020. http://d-nb.info/1205821899/34.
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Deng, Ni. "A secure, payment-based email delivery system." CSUSB ScholarWorks, 2005. https://scholarworks.lib.csusb.edu/etd-project/2909.
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Sharma, Divya. "Drug Delivery Systems for Treatment of Diabetes Mellitus." Diss., North Dakota State University, 2019. https://hdl.handle.net/10365/31745.
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Daily injections for basal insulin therapy are far from ideal resulting in hypo/hyperglycemic episodes associated with fatal complications in type-1 diabetes patients. The purpose of this study was to develop a thermosensitive copolymer-based in situ depot forming delivery system to provide controlled release of insulin for extended duration following a single subcutaneous injection, closely mimicking physiological basal insulin requirement. Size and nature of the incorporated therapeutic were observed to affect the release profile of insulin. Modification with zinc and chitosan preserved thermal, conformational, and chemical stability of insulin during the entire duration of storage (up to 9 months at 4 °C) and release (up to 3 months at 37 °C). In vivo, daily administration of long-acting insulin, glargine, resulted in fluctuating blood glucose levels between 91 – 443 mg/dL in type 1 diabetic rats. However, single administration of oleic acid-grafted-chitosan-zinc-insulin complexes incorporated in copolymer formulation demonstrated slow diffusion of insulin complexes maintaining peak-free basal insulin level of 21 mU/L for 91 days. Sustained release of basal insulin also correlated with efficient glycemic control (blood glucose <120 mg/dL), prevention of diabetic ketoacidosis and absence of cataract development, unlike other treatment groups. The suggested controlled basal insulin delivery system has the potential to significantly improve patient compliance by improving glycemic control and eliminating life-threatening diabetes complications.
Furthermore, oleic acid-grafted-chitosan (CO) nanomicelles were investigated as a non-viral vector to deliver plasmid DNA encoding short hairpin RNA (shRNA) against pro-inflammatory cytokines to adipose tissue macrophages and adipocytes for the treatment of insulin resistance. Nanomicelles modified using mannose (COM) and adipose homing peptide (AHP) (COA) showed significantly higher uptake and transfection efficiency in inflamed macrophages- adipocytes co culture owing to glucose transporter-1 and prohibitin receptor mediated internalization, respectively. Ligand modified nanomicelles loaded with shRNA against tumor necrosis factor alpha (COM-TNFα) and monocyte chemoattractant protein-1 (COA-MCP1) demonstrated significant attenuation of pro-inflammatory cytokines and improved insulin sensitivity and glucose tolerance in obese-diabetic mice for six weeks post treatment with single dose of optimized formulation. Overall, chitosan nanomicelles mediated targeted gene therapy can help attenuate inflammation, the chief underlying cause of insulin resistance, thereby helping reverse the progression of diabetes.National Institutes of Health (NIH) grant R15GM114701
ND EPSCoR seed award FAR0030636
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Oh, Sejin. "Development of mucus permeating nanoparticles-based drug delivery systems." Doctoral thesis, Universitat Ramon Llull, 2016. http://hdl.handle.net/10803/382626.
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Existeix un interès creixent, tant en el món acadèmic com en la recerca industrial en el desenvolupament de sistemes d’alliberament de fàrmacs macromoleculars (proteïnes, pèptids, oligonucleotids) capaços de travessar la mucosa. En aquest sentit, la utilització de vectors sintètics per a l’alliberament de les esmentades macromolècules, permet disposar d’una plataforma versàtil i altament eficient. Tanmateix, la capa de mucosa amb propietats adhesives i altament viscoelàstica, té una elevada capacitat d’atrapar i eliminar qualsevol substància estranya que quedi adherida sobre la seva superfície, limitant, de forma evident, la eficàcia de qualsevol tractament
Aquesta Tesi es centra en el desenvolupament de sistemes d’alliberament de DNA, dissenyats a mida, que presenten una elevada estabilitat i eficàcia de transfecció amb un nivell molt baix de toxicitat i molt important en el context de la tesi, una capacitat de permeació a través de la mucosa. A més la tesi també es centra en el disseny i el desenvolupament de mètodes i tècniques in vitro que ajudin a una millor selecció de sistemes eficients d’alliberament a través de la mucosa.
Així s’ha desenvolupat un mètode simple i eficient, basat en la utilització de una microbalança de quartz amb dissipació (QCM-D). Aquest mètode ha permès avaluar la interacció de polímers i nanopartícules amb una capa de mucina. Els resultats obtinguts amb el mètode desenvolupat han permés dissenyar sistemes de nanopartícules amb un potencial més gran de permeació a través de la mucosa. Aquesta tècnica d’alta sensibilitat també ha ofert la possibilitat d’avaluar las dos propietats oposades, el coneixement de les quals és necessari per un correcte disseny de sistemes cpaços de creuar la mucosa: mucoadhesió vs mucopenetració.
Los Poly(β-amino ester)s (PBAEs) s’han proposat com a sistemes biodegradables capaços de formar nanopartícules, per complexació amb DNA, que presenten una elevada capacitat de transfecció. Tanmateix, mostren problemes d’estabilitat en condicions fisiològiques i són incapaços de travessar la capa de mucosa. En aquesta tesi es descriu una nova solució en la preparació de les formulacions dels nanocomplejos basada en la utilització de recobriments que estabilitzen les nanopartícules i augmenten la seva permeabilitat. Els recubrimeintos proposats inclutyen: i) sucres (sucroses, trhalosa i manitol), ii) quitosà sense modificar de 22 KDa i amb 60-120 kDa, iii) quitosan modificat amb àcid tioglicolidoi i iv) acid poliacrílic-bromelaina. Totes les noves formulacions s’han avaluat amb diferents quantitat de recobriment. S’han determinat les seves propietats fisicoquímiques i la seva eficàcia de transfecció i citotoxicitat en front de cèl.lules COS-7. S’ha estudiat La difusió de las partícules a través de la mucosa gàstrica de porc utilitzant diferents tècniques com el tub rotatori de silicona o el multiple particle tracking (MPT).
Els resultats obtinguts han mostrat la superior estabilitat, eficàcia de transfecció i permeabilitat sobre la mucosa de las noves formulacions dissenyades.Existe un interés creciente, tanto en el mundo académico como en la investigación industrial en el desarrollo de sistemas de liberación de fármacos macromoleculares (proteínas, péptidos, oligonucleótidos) capaces de atravesar la mucosa. En este sentido, la utilización de vectores sintéticos para la liberación de dichas macromoléculas, permite disponer de una plataforma versátil y altamente eficiente. Sin embargo, la capa de mucosa con propiedades adhesivas y altamente viscoelástica, tiene una elevada capacidad de atrapar y eliminar cualquier sustancia extraña que quede adherida sobre su superficie, limitando, de forma evidente, la eficacia de cualquier tratamiento Esta Tesis se centra en el desarrollo de sistemas de liberación de ADN, diseñados a medida, que presentan una elevada estabilidad y eficacia de transfección con un nivel muy bajo de toxicidad y muy importante en el contexto de la tesis, una capacidad de permeación a través de la mucosa. Además la tesis también se centra en el diseño y el desarrollo de métodos y técnicas in vitro que ayuden a una mejor selección de sistemas eficientes de liberación a través de la mucosa. Así se ha desarrollado un método simple y eficiente, basado en la utilización de una microbalanza de cuarzo con disipación (QCM-D). Este método ha permitido evaluar la interacción de polímeros y nanopartículas con una capa de mucina. Los resultados obtenidos con el método desarrollado han permitido diseñar sistemas de nanopartículas con un mayor potencial de permeación a través de la mucosa. Esta técnica de alta sensibilidad también ha ofrecido la posibilidad de evaluar las dos propiedades opuestas, el conocimiento de las cuales es necesario para un correcto diseño de sistemas cpaços de cruzar la mucosa: mucoadhesió vs mucopenetració. Los Poly (β-amino ester)s (PBAEs) se han propuesto como sistemas biodegradables capaces de formar nanopartículas, por complejación con ADN, que presentan una elevada capacidad de transfección. Sin embargo, muestran problemas de estabilidad en condiciones fisiológicas y son incapaces de atravesar la capa de mucosa. En esta tesis se describe una nueva solución en la preparación de las formulaciones de los nanocomplejos basada en la utilización de recubrimientos que estabilizan las nanopartículas y aumentan su permeabilidad. Los recubrimeintos propuestos inclutyen: i) azúcares (sucrosa, trhalosa y manitol), ii) quitosano sin modificar de 22 KDa y con 60-120 kDa, iii) quitosano modificado con ácido tioglicólico y iv) ácido poliacrílico-bromelaina. Todas las nuevas formulaciones se han evaluado con diferentes cantidades de recubrimiento. Se han determinado sus propiedades fisicoquímicas y su eficacia de transfección y citotoxicidad frente a células COS-7. Se ha estudiado La difusión de las partículas a través de la mucosa gástrica de cerdo utilizando diferentes técnicas como el tubo rotatorio de silicona o el múltiple particle tracking (MPT). Los resultados obtenidos han mostrado superior estabilidad, eficacia de transfección y permeabilidad sobre la mucosa de las nuevas formulaciones diseñadas.
Mucus penetrating nanoparticle-based delivery systems of macromolecular drugs are currently receiving increasing attention in both academic and industrial research. Synthetic delivery systems provide highly suitable and tunable platform for the delivery of the macromolecules. However, a highly viscoelastic and adhesive mucus layer generally traps and rapidly removes most foreign substance from the mucosal surfaces, thereby limiting effectiveness of these nanocarriers. This Thesis is addressed to the development of engineering DNA delivery systems capable of high stability and transfection efficiency with low toxicity, and quickly crossing the mucus layer. Moreover, this Thesis is focused on design and development of methods and techniques in vitro in order to select more efficient delivery systems. A simple and efficient method, based on the use of the quartz crystal microbalance with dissipation (QCM-D) technique, is developed and evaluated the interaction of the polymers and nanoparticles with the mucin layer, resulting in the development of nanoparticle-based delivery systems to mucosal tissue. This highly sensitive technique also offers to evaluate the two opposing properties, needed for the design of efficient mucous permeation systems: mucoadhesion vs mucus penetration. Poly(β-amino ester)s (PBAEs) are currently considered of great interest as biodegradable polymeric carriers of DNA delivery, but they present limited stability in physiological conditions and the inability to penetrate the mucus layer. In this Thesis, we describe a novel surface-modified formulation of DNA delivery systems consisting of PBAE/DNA complexes and the coating agents, including: i) sugars (sucrose, trehalose or mannitol), ii) unmodified chitosan with a 22 kDa (CS) and a with a 60-120 kDa (CSM), iii) chitosan-thioglycolic acid (CS-TGA), and iv) poly(acrylic acid)-bromelain (PAA-BRO) conjugates. All novel formulations formed with different amounts of the coating agents are evaluated the physicochemical properties. The influence of coating agents on transfection efficiency and cytotoxicity is evaluated in COS-7 cells. Particle diffusion through porcine intestinal mucus (PImucus) is assessed by either rotating silicone tube technique or multiple particle tracking (MPT). The results highlight the superior stability, transfection efficiency and mucus permeability of the novel nanoparticle-based drug delivery systems. The effect of the amount of coating agents is also discussed.
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Dua, Pinky. "Model based and parametric control for drug delivery systems." Thesis, Imperial College London, 2005. http://hdl.handle.net/10044/1/8040.
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Dixon, John Robert. "Examining the impacts of Web-based education delivery systems." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ58335.pdf.
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Schultze, Jennifer [Verfasser]. "Polymer-Based Systems for Drug Delivery Studies / Jennifer Schultze." Mainz : Universitätsbibliothek Mainz, 2019. http://d-nb.info/1186179627/34.
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Elahrash, K. S. "Some physical studies with polymer based drug delivery systems." Thesis, University of Brighton, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.354875.
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Mohd, Azmi Mohd Azraie Bin. "Integrated silicon nanowire biosensor and MEMS based delivery systems." Thesis, Swansea University, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.678641.
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Abodinar, Atiga Emhemed. "Construction of potential drug delivery systems based on polysaccharides." Thesis, University of Huddersfield, 2016. http://eprints.hud.ac.uk/id/eprint/32608/.
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Enhancement of the drug efficacy and elimination of the side effects resulting from drug overdoses are an essential aspect in drug therapy. To achieve these demands two general guidelines have been used; producing new drugs with higher selectivity and therefore less side effects and improving controlled/sustained drug delivery agents based on polymers. Thus, the relationship between the active pharmaceutical ingredient and the polymeric system is important in the development of a drug delivery system and several considerations need to be taken in to account, for example the polymer should be biocompatible, biodegradable, and non-toxic and physiochemical properties. Because mucus is the first barrier with which food and drugs can interact with and diffuse through to be absorbed and enter the circulatory system, characterisation of mucin is an essential step towards establishing suitable pharmaceutical excipients. Therefore, the aim of the present study was to investigate the potential to construct and study drug delivery systems based on polysaccharides. The physicochemical characterisation of extensively degraded pig gastric mucin was studied and revealed that this type of mucin contains: protein, carbohydrate (Fuc, Gal, GalN, GlcN) and sialic acid, which provides the negative charges that becomes progressively stronger with increasing pH. The measurements of viscosity vs. shear rate showed that mucin has a shear thinning behaviour and a relatively low viscosity which is consistent with a high critical overlap concentration (c*), small hydrodynamic size and hence compact structure. The insight in to the compositional, hydrodynamic and viscoelastic properties support the understanding of mucin interactions with polysaccharide based drug delivery systems. Several polysaccharides including chitosan (Cs), two grade of alginates; high guluronate alginate (HGA) and low guluronate alginate (LGA) (which differ in structural conformation) and two kinds of pectin; high methoxyl pectin (HMP) and low methoxyl pectin (LMP) (with different degrees of esterification) have been characterised. The structure of these polysaccharides as powder have been studied; Fourier transform infrared spectroscopy ) findings indicate the structure and the function group for each polysaccharide whereas powder X-ray diffraction measurements displays that all the polysaccharide which were analysed are amorphous in nature except LMP which has a number of sharp crystalline peaks. In addition, solution properties of these polysaccharides such as zeta potential and intrinsic viscosity were investigated at several ionic strengths and pH. Furthermore the molecular weights were evaluated based on intrinsic viscosity and the Smidsrød-Haug stiffness parameter (B) and intrinsic persistence length (Lp) were estimated using the novel ionic strength dependency of zeta potential method and intrinsic viscosity (traditional method). The interaction between polysaccharides and pig gastric mucin were evaluated based on relative viscosity. It has been suggested that polysaccharide–mucin interactions are not only driven by electrostatic forces, but also by the molecular weight, conformation and flexibility of the polymer also played significant roles. As the mucin-HGA system displayed exceptionally high viscosity, the viscoelastic properties of this system were extensively studied. The mechanical spectra of the mucin-HGA blends indicate that with the exception of the system involving only HGA (0 % mucin) and 60 % mucin, all mixtures including mucin itself displayed typical ‘weak gel’ rheological behaviour and the gel became stronger with decreasing HGA content in the system. Moreover 80 % of mucin was successfully encapsulated within phospholipids bilayer using liposomal encapsulation technology. The liposomal vesicles with encapsulated mucin display larger sizes than the control vesicles (prepared in DI water) this may be due to the electrostatic interaction between mucin molecules and phospholipid which is the main component the vesicles. In the final part of the thesis the hydrogel containing chitosan and naturally occurring polyanions and its potential for drug release were studied. Chitosan - polyanion (HGA, LGA, HMP and LMP) hydrogels complexes were successfully prepared (in acetate buffer 0.05M, 4.3 pH) at various ratios (10 %, 30 %, 50 %, 70 % 90 % of Cs) using the ionotropic gelation method. The freeze dried hydrogels were characterized by FT-IR and XRD and the results confirmed the electrostatic interactions between chitosan and polyanions at all ratios and percentage yield of hydrogel ζ and ηsp results of the supernatant was determined and it was found that the optimum ratios 3:7 and 1:1 of chitosan-pectins and chitosan-alginates respectively. The hydrogels of ideal ratios were studied by determining zeta potential, particles size, water uptake, morphology by scanning electron microscopy for freeze dried hydrogels and optical microscopy analysis for homogenous suspension. In addition, dynamic small deformation oscillatory measurements and adhesion property were studied. Finally, ibuprofen was successfully encapsulated by the chitosan-polyanion hydrogel complexes and the encapsulation efficiency of the formulations was calculated. Finally the drug release behaviour of the formulations was in vitro assessed over the time. The findings demonstrated that HMP and LGA hydrogels displayed the highest percentage of retained ibuprofen followed by HGA and LMP. This could be attributed to the fibrous appearance small size of pores which may impedes movements of entrapped molecules.
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Tang, Qiong. "Multifunctional Natural Material-based Delivery Systems for Gene Therapy." University of Akron / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=akron1415382826.
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Brinkmann, Joscha [Verfasser]. "Thermodynamics of Lipid-Based Drug Delivery Systems / Joscha Brinkmann." München : Verlag Dr. Hut, 2021. http://d-nb.info/1238423043/34.
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Hwang, Jason Jayjoon. "Hyaluronic acid hydrogel microspheres for delivery of protein therapeutics /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/7983.
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Soane, Robert J. "Bioadhesive polymers as intranasal drug delivery systems for peptide and protein drugs." Thesis, University of Nottingham, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298078.
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Madeira, do Ó. João. "Applications of glycopolymer libraries as protein aggregation modulators and drug delivery systems." Thesis, University of Nottingham, 2016. http://eprints.nottingham.ac.uk/38014/.
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The biopharmaceutical market has been on the rise for the past two decades and is expected to continue to excel, currently presenting a growing rate of more than double than conventional pharma. Traditionally this growth has been hindered by multiple formulation issues such as poor bioavailability and poor stability. Consequently, the drive to optimise the stability of protein drug candidates via formulation impels the need for development of novel excipients. Novel glycopolymer excipients were reported to confer improved protein stability in selected cases. Nonetheless,their structure-function relationship and wider applicability remain largely unknown. Here we report the synthesis of glycopolymers with different molecular architectures based on mannose, galactose, arabinose, N-acetyl glucosamine, lactose and trehalose, and nvestigate their utility as excipients for the solution formulation of a monoclonal antibody (mAb). In this thesis work the physical stability of selected antibodies was measured as the unfolding transition temperature (Tm) and aggregation onset temperature (Tagg), as a function of glycopolymer properties, such as the nature of sugar repeating unit, macromolecular architecture and concentration. Results show that, in contrast to the stabilising effect of the corresponding mono- and di-saccharide constituents, both linear and 4-arm star glycopolymers generally destabilised the antibody, decreasing both Tm and Tagg. Accelerated stability studies of a concentrated mAb solution followed the same trend, where an increasing glycopolymer:mAb molar ratio generally decreased the percentage monomer(i.e. increased soluble aggregates). Importantly, trehalose-based glycopolymers further generated visible aggregates that could not be predicted from Tm or Tagg data. The data demonstrate a complex interplay of sugar chemistry and solution concentration of synthetic glycopolymers on their modulation of protein conformational stability and aggregation propensity. The mechanisms involved in protein:glycopolymer interaction, both in solution and dry state were further investigated, thus unravelling the behaviour reported in terms of protein stabilisation. Finally, the glycopolymers were studied as drug delivery systems, acting as solubility enhancers for hydrophobic species in aqueous solutions, through the use of extrinsic fluorescent dyes.
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Veldhoen, Marc. "Modifying T cell differentiation via protein based delivery of signalling attenuators." Thesis, Open University, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.273353.
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Ayensu, Isaac. "Development of novel formulations for mucosal delivery of protein based drugs." Thesis, University of Greenwich, 2012. http://gala.gre.ac.uk/9807/.
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Stable mucoadhesive lyophilised chitosan and thiolated chitosan xerogels have been developed for potential delivery of proteins via the buccal mucosa. Membrane dialysis to eliminate sodium acetate (NaAc) and annealing during lyophilisation cycle (developed by differential scanning calorimetry; DSC) were critical for obtaining optimised porous xerogels. Based on characteristic performance and structural integrity, xerogels containing 10 % (per polymer weight) each of plasticizer (glycerol) and cryoprotectant (D-mannitol) were loaded with bovine serum albumin (BSA) and insulin (INS) as model drugs for further development. The optimised xerogels were loaded with enzyme inhibitor (EI) and permeation enhancer (PE) to enhance permeability of the buccal mucosa and backed with impervious ethylcellulose (EC) laminate to ensure unidirectional release. Characterisation of xerogels using 1HNMR and ATR-FT-IR spectroscopy confirmed the functional groups in chitosan and TG-chitosan. The amount of thiol groups on TG-chitosan was quantified by Ellman’s reaction with polymer molecular weight monitoring by gel permeation chromatography (GPC). The stability of the secondary structures of BSA and INS were by ATR-FT-IR and circular dichroism (CD) while xerogel crystallinity was examined by XRPD. SEM micrographs showed highly porous xerogels due to annealing which allowed for high drug loading and hydration capacities of the dialysed and annealed xerogels which also exhibited optimal moisture content for maintaining protein stability. Disulphide bond formation in thiolated xerogels however limited the hydration capacity. Storage at 25 °C/ 60 % RH for six months led to protein instability while storage at 5 °C maintained protein stability. 2% mucin concentration was found optimum for mucoadhesion studies of the chitosan based xerogels. EI (glutathione; GSH and aprotinin; APR) effect on mucoadhesion was concentration dependent and inhibitor specific. In vitro BSA release profiles from annealed xerogels were similar and significantly higher than non-annealed xerogels but were not affected by thiolation. Crystalline NaAc in the undialysed xerogel led to a three-fold reduction in BSA release. Significant reductions in BSA and INS release were also observed with the addition of EIs to TG-chitosan-BSA and TG-chitosan-INS xerogel respectively. The drug dissolution data from xerogels fitted best with model dependent First order, Hixson-Crowell and Korsmeyer-Peppas equations. Permeation studies’ using EpiOralTM showed 12- to 14-fold increase in BSA permeation but was reduced by GSH for both BSA and INS loaded xerogels. APR containing xerogel enhanced INS permeation through sheep buccal membrane and demonstrated a good linear correlation with EpiOralTM. These results demonstrate the potential application of lyophilised chitosan and thiolated chitosan xerogels for buccal mucosa delivery of proteins with improved mucoadhesion, penetration enhancing and enzyme inhibition characteristics.
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Booth, Ronald L. "An Information Systems Project Delivery Methodology for Implementing Web-Based Program Management Systems." NSUWorks, 2003. http://nsuworks.nova.edu/gscis_etd/420.
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In this study the researcher applied an Information Systems Project Delivery Methodology (ISPDM) for implementing a Web-based Program Management System in an organization that did not have one. The problem investigated in this study was the difficulty encountered when organizations implement ISPDMs. The research questions were (1) what is the role of each of Roberts' et al. five factors in the implementation of an ISPDM? And (2) how effective is a Web-based program management system implemented using an ISPDM in meeting the participants desired outcomes? The general approach utilized to address the research questions was to describe the implementation of a Web-based program management ISPDM using a single descriptive case study. A survey, focus group, and usability testing were utilized at three different stages of the Web-based program management module's implementation.
In conducting this study research, multiple sources of data were collected to develop an in-depth description of the case as it developed. The open-ended survey was given at three different points, the beginning, the middle and the end of the ISPDM Web based program management module implementation. A focus group was conducted for planning evaluation to assess the participant's desired outcomes for the Web-based program management system. A focus group for in-process evaluation assessed the extent to which the Web-based program management module achieved the outcome measures. A focus group for summative evaluation determined whether or not the final product met the expectations of the users. In addition, a usability survey was conducted in conjunction with the in-process and summative evaluation focus groups.
The results of this study indicated the role of organizational transition when implementing a Web-based program management system using an ISPDM is to provide training, education, and communications. The role of functional management involvement/support during the implementation process is to provide resources and lead the process of adopting the new methodology. The role of the ISPDM during the transition stage is to communicate the change and to foster cultural integration, provide a framework for using the product, and to provide training. The role of the use of software development models in the implementation process is to provide guidelines, framework, metrics, and to lend credibility to the value of the methodology. The role of external support during the implementation process is to provide an industry-wide knowledge base, oversight, and an independent review of the new methodology.
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Stasko, Nathan Allan Schoenfisch Mark H. "Synthesis and characterization of dendrimer-based nitric oxide delivery systems." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2007. http://dc.lib.unc.edu/u?/etd,1421.
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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2007.Title from electronic title page (viewed Apr. 25, 2008). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Chemistry." Discipline: Chemistry; Department/School: Chemistry.
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Mistry, Ajay Ramanlal. "Development of non-viral gene delivery systems based on HMG1." Thesis, Imperial College London, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368705.
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Bergin, Paul Michael. "Approaches to functionalised amine-based ligands for radiopharmaceutical delivery systems." Thesis, University of Southampton, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.409852.
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Iemsam-Arng, J. "Poly(ethylene) glycol based delivery systems for nucleic acid therapies." Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1381001/.
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Our work is aimed at developing a synthetic biocompatible gene and siRNA delivery system for the treatment of primary and metastatic tumours. To facilitate delivery of nucleic acid based drugs into the cell, one strategy is to formulate the naked gene with an amine based non-viral gene delivery system via the counterion interaction. The delivery systems including 4arm-PEG-amine, 4arm-PEG-N-2-ethylamine, 8arm-PEG-amine and 8arm-PEG-N-2-ethylamine were synthesised, characterised and complexed with a reporter gene (β-gal plasmid DNA) in phosphate buffer pH 6.0. The resulting complexes were sized and their zeta potential measured (Malvern Zetasizer 3000HS, Malvern Instruments, UK). The complexes were also imaged using transmission electron microscopy and characterised for DNA binding and DNA protection using gel electrophoresis and the ethidium bromide displacement assay. The in vitro transfection efficiency and cell cytotoxicity of the complexes were determined in the A431 and HeLa cells. Additionally, in vivo therapeutic studies in female nude tumour bearing mice were carried out. A promising DNA-polymer complex of 4arm-PEG-N-2-ethylamine produced a complex of 200-300 nm in diameter (polydispersity < 0.6). Complexes had a zeta potential of +19.8 mV (n=3) and were spherical, fibrillar and toroidal in shape. The new gene delivery complex protected DNA from degradation in serum up to 2 hours and was as efficient as poly(ethylenimine) (PEI) in transfecting the A431 cell line, but it was more than 3 orders of magnitude less cytotoxic than PEI. In vivo a gene medicine, comprising the polymer and the tumour necrosis factor alpha gene, was tumouricidal. When complexed with siRNA, the siRNA polymer complex demonstrated a trend of gene silencing activity. A new synthetic gene delivery polymer of 4arm-PEG-N-2-ethylamine has been synthesised. This polymer is biocompatible to cells and is an efficient in vitro and in vivo gene transfer agent.
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Culcuoglu, Mustafa U. "Reengineering Community Based Chronic Care Delivery Systems: Theory and Applications." University of Akron / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=akron1627573050496332.
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Oladiran, Gbolahan S. "Development and formulation of wax-based transdermal drug delivery systems." Thesis, Aston University, 2008. http://publications.aston.ac.uk/11060/.
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Topical and transdermal formulations are promising platforms for the delivery of drugs. A unit dose topical or transdermal drug delivery system that optimises the solubility of drugs within the vehicle provides a novel dosage form for efficacious delivery that also offers a simple manufacture technique is desirable. This study used Witepsol® H15 wax as a abase for the delivery system. One aspect of this project involved determination of the solubility of ibuprofen, flurbiprofen and naproxen in the was using microscopy, Higuchi release kinetics, HyperDSC and mathematical modelling techniques. Correlations between the results obtained via these techniques were noted with additional merits such as provision of valuable information on drug release kinetics and possible interactions between the drug and excipients. A second aspect of this project involved the incorporation of additional excipients: Tween 20 (T), Carbopol®971 (C) and menthol (M) to the wax formulation. On in vitro permeation through porcine skin, the preferred formulations were: ibuprofen (5% w/w) within Witepsol®H15 + 1% w/w T; flurbiprofen (10% w/w) within Witepsol®H15 + 1% w/w T; naproxen (5% w/w) within Witepsol®H15 + 1% w/w T + 1% C and sodium diclofenac (10% w/w) within Witepsol®H15 + 1% w/w T + 1% w/w T + 1% w/w C + 5% w/w M. Unit dose transdermal tablets containing ibuprofen and diclofenac were produced with improved flux compared to marketed products; Voltarol Emugel® demonstrated flux of 1.68x10-3 cm/h compared to 123 x 10-3 cm/h for the optimised product as detailed above; Ibugel Forte® demonstrated a permeation coefficient value of 7.65 x 10-3 cm/h compared to 8.69 x 10-3 cm/h for the optimised product as described above.
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Inaba, Hiroshi. "Structural design of cell-penetrating protein needles toward development of intracellular delivery systems." 京都大学 (Kyoto University), 2015. http://hdl.handle.net/2433/195979.
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Olszewska, Wieslawa. "The immunogenicity of vaccine delivery systems incorporating epitopes from measles virus fusion protein." Thesis, London School of Hygiene and Tropical Medicine (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.251659.
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Nolan, Christine Marie. "Microgel Based Materials for Controlled Macromolecule Delivery." Diss., Georgia Institute of Technology, 2005. http://hdl.handle.net/1853/6874.
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This dissertation focuses on utilization of poly(N-isopropylacylamide) (pNIPAm) based mirogels for regulated macromolecule drug delivery applications. There is particular emphasis on incorporation of stimuli responsive materials into multi-layer thin film constructs with the main goal being fabrication of highly functional materials with tunable release characteristics. Chapter 1 gives a broad overview of hydrogel and microgel materials focusing on fundamental properties of pNIPAm derived materials. Chapter 2 illustrates the progression of controlled macromolecule release from hydrogel and microgel materials and sets up the scope of this thesis work. Chapter 3 details studies on thermally modulated insulin release from microgel thin films where extended pulsatile release capabilities are shown. Chapters 4 and 5 focus on more fundamental synthesis and characterization studies of PEG and acrylic acid modified pNIPAm microgels that could ultimately lead to the design of protein loaded microgel films with tunable release characteristics. Chapter 6 illustrates fundamental macromolecule loading strategies, which could also prove useful in future protein drug delivery design using stimuli responsive networks. Chapter 7 concentrates on direct insulin release studies that probe the interaction between entrapped and freely diffusing protein and microgels. These model experiments could prove useful in design of tunable macromolecule drug release from functionally modified microgels and could aid in the tailored design of peptide-loaded microgel thin films. Chapter 8 discusses the future outlook of controlled macromolecule release from microgel based materials.
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Scally, David James. "Novel polyethylene glycol based drug delivery systems : a calorimetric and QASAR based study." Thesis, University of Kent, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.282425.
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Wong, Ling Wai. "Molecular delivery system based on the nanoporous zeolite microstructures /." View abstract or full-text, 2006. http://library.ust.hk/cgi/db/thesis.pl?BIEN%202006%20WONG.
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Wang, Nick X. "Controlled Delivery of Protein Therapeutics for HIV Prevention." Case Western Reserve University School of Graduate Studies / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=case1327614039.
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Pan, Xiaogang. "Design and evaluation of lipid based delivery systems for delivery of small molecules and macro-molecular nucleotides based therapeutic agents." Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1164679618.
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Sankaranarayanan, Thampi Sajeesh. "Development of advanced drug delivery systems based on polymethacrylic acid nano/microparticles for oral insulin delivery." Paris 11, 2010. http://www.theses.fr/2010PA114805.
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L’étude a portée sur le développement de micro- et nanoparticules polymères destinées à l’administration orale d’insuline. Une méthode de polymérisation radicalaire a été optimisée pour formuler des micro et des nanoparticules à base d’un polymère formant des hydrogels, le poly(acide de méthacrylique). Les particules ont ensuite été modifiées par greffage de résidus cystéine pour introduire des fonctions thiol en vue de renforcer les propriétés de bioadhésion et de promoteur d’adsorption des systèmes obtenus. Les particules ont montré des propriétés intéressantes de chargement en insuline et la libération se fait selon un mode de libération pH sensible. En effet, alors que l’insuline est majoritairement retenue dans la forme pharmaceutique à pH acide correspondant à un milieu gastrique, elle est libérée à un pH neutre voire légèrement basique retrouvé au niveau de l’intestin. Les systèmes ont montré une bonne capacité à améliorer le passage de l’épithélium intestinal sur des monocouches de cellules Caco 2 et sur de l’intestin isolé monté en chambres de Ussing. Au final, ces systèmes ont permis d’induire in vivo une réduction de la glycémie chez des animaux diabétiques et après une administration orale. Les essais menés sur des insulines modifiées ont permis d’identifier une stratégie de modification intéressante basée sur l’association de l’hormone à une cyclodextrine. En revanche, nos résultats suggèrent que la PEGylation de l’insuline n’apporte aucun bénéficeThe work carried out in this thesis was aimed to develop polymer micro- and nanoparticles for the oral administration of insulin. A method of radical polymerization was optimized to design micro and nanoparticles with a hydrogel forming polymer, poly(methacrylic acid) (PMAA). The particles were further modified by the grafting of cystein residues in order to introduce thiol functions which are believed to reinforce mucoadhesive and permeation enhancing properties of the formulation. The particles showed interesting loading properties for insulin and the release of the hormone was found to be pH dependent. Although insulin was mainly retained by the hydrogel particle in releasing medium mimicking the gastric environment, the hormone was released in conditions found in the intestine. The formulated systems have shown to improve the absorption of insulin through the intestinal mucosa in in vitro models including Caco 2 cell monolayers and the Ussing chambers. The microparticles selected from the in vitro experiments for in vivo studies have shown a capacity to deliver active insulin through the oral route to diabetic rats producing a reduction of the glycemia. Tests performed with modified insulin have allowed to identify that among the two strategies followed, this consisting on the association of insulin with a cyclodextrin was the most promising while the one based on the formation of an insulin-PEG conjugate did not brought any benefice