The experiments performed for this research were completed to produce solid cerium oxide microspheres by an internal gelation sol-gel process. The motivation for this work was to develop a process that would enable the fabrication of a storage or transmutation form for the plutonium and transuranics (TRU) from the Uranium Extraction Plus (UREX ) used fuel reprocessing process. This process is being investigated by the Department of Energy (DOE) and the Advanced Fuel Cycles Initiative (AFCI) through the Nuclear Energy Research Initiative. The internal gelation production of cerium oxide involves the combination of hexamethylenetetramine (HMTA), urea, and cerium nitrate solutions at ~100oC. Microspheres were produced by injection of a broth solution into a flowing stream of hot silicone oil. The captured microspheres were aged, washed, and then underwent Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), and XRay Diffraction (XRD) analysis. The process variables examined in this study include the concentrations of HMTA, urea and cerium nitrate, the process temperature, the postgelation aging time, and the product washing conditions. Over a series of 70 experiments, it was determined that a broth solution containing a mixture of 1.45 M cerium nitrate and 1.65 M HMTA and urea (1:1 ratio) solutions produced the best cerium oxide microspheres. The spheres were aged for 30 to 60 minutes and then washed in hexane to remove the silicone oil and a subsequent series of ammonium hydroxide washes to remove unreacted product and to fully gel the microspheres. Through DSC analysis it was determined that excess wash or unreacted product may be removed by an exothermic reaction at approximately 200oC. The XRD analysis of unheated spheres showed the presence of cerium oxide with additional cerium-bearing organics. Following heating, the microspheres were completely converted to cerium oxide.

Thesis (Ph.D.)--McMaster University (Canada), 1994. / Source: Dissertation Abstracts International, Volume: 56-08, Section: B, page: 4349. Adviser: H. D. H. Stover.

Thesis (Ph. D.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 89-96) Also available in print.

Thesis (Ph.D. in Pharmaceutical Sciences) -- University of Colorado at Denver and Health Sciences Center, 2005. / Typescript. Includes bibliographical references (leaves 86-92). Free to UCDHSC affiliates. Online version available via ProQuest Digital Dissertations;

Drugs can be made up of nucleic acids, sugars, small organic and inorganic compounds, peptides, and large macromolecules. Drug therapy can be optimized by controlled delivery systems that release an appropriate dose to the site of action, extend the duration of delivery, reduce administration sessions, and can target a precise site of activity. An advanced method of controlled drug delivery is through injectable polymeric biomaterial microparticles that entrap drugs within their matrix for slow release (1-6 months). Surface morphology of polymer microparticles is known to affect drug release; however, it is often reported in qualitative terms only. In this thesis, a mastery over the controlled fabrication of biodegradable poly (ε-caprolactone) (PCL) microspheres is shown, as well as their characterization using different imaging conditions/techniques of the scanning electron microscope (SEM). Retinoic acid (RA), a morphogenic molecule, is encapsulated to create RA/PCL microspheres that are used to successfully deliver drug to human induced pluripotent stem cell aggregates. Furthermore, this works reports the creation of variable surface morphology PCL microspheres and their characterization via size analysis and stereo-microscopy. A rough morphology candidate is identified and selected for 3D SEM surface model reconstruction via a computer vision technique. Surface studies via SEM have a lot of potential to advance the development of these particles. The 3D model first reported here serves as foundation for quantitative surface morphology measurements. / Graduate

Made available in DSpace on 2014-10-09T12:54:31Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:08:01Z (GMT). No. of bitstreams: 0 / Dissertação (Mestrado) / IPEN/D / Instituto de Pesquisas Energéticas e Nucleares - IPEN/CNEN-SP

Orientador: Teresa Dib Zambon Atvars / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-16T13:58:18Z (GMT). No. of bitstreams: 1 Zalloum_NeifeLilian_D.pdf: 6371493 bytes, checksum: 34b58b4e3f06b8bb42b89ffa183838c1 (MD5) Previous issue date: 2007 / Resumo: Desenvolveu-se, neste trabalho, uma metodologia que permitiu conhecer detalhes intermoleculares da microencapsulação, fundamentais na definição de parâmetros que controlam este processo. Foram preparadas microesferas biodegradáveis de poli(hidroxibutirato-hidroxivalerato) (P(HB-HV)), por meio de emulsificação o/w com evaporação de solvente, de interação controlada com os marcadores fluorescentes. Os estudos foram conduzidos de forma a se avaliar como o polímero e alguns parâmetros afetam as propriedades finais das microesferas, tais como concentração de PVA, velocidade de agitação da emulsão, número de ciclos de lavagem durante a centrifugação, presença do ativo a ser encapsulado (cumarina, cumarina-6 e pireno), e massa molar do polímero (130 e 450 kg mol). As microesferas poliméricas foram submetidas à análise de microscopia eletrônica de varredura para análise morfológica e de distribuição de tamanho de partículas; de potencial-zeta para análise da carga superficial; de microscopia de fluorescência confocal para confirmar a encapsulação; estudos fotofísicos e de liberação. Os parâmetros que mais afetaram o diâmetro médio e a distribuição de tamanhos das microesferas foram a concentração de PVA e a velocidade de agitação durante a emulsificação. Medidas de potencial-zeta permitiram colocar as intensidades de carga superficial na ordem microesferas+pireno < micropartículas vazias < microesferas+cumarina-6. As eficiências de encapsulação (de 95% e 17% para as microesferas contendo cumarina-6 e pireno, respectivamente) indicaram a ocorrência de diferentes tipos de interações polímero-fluoróforo. Imagens de microscopia de fluorescência confocal confirmaram a formação de agregados de cumarina-6 no interior das microesferas, ao contrário do pireno, que formou excímeros nas camadas mais externas das partículas. Estudos de liberação mostraram que as microesferas de P(HB-HV) são polares e que a difusão da cumarina-6 depende do tamanho das micropartículas e das interações eletrostáticas entre polímerofluoróforo. A difusão do pireno depende somente das interações hidrofóbicas com o polímero / Abstract: In this research was developed a methodology, which allowed microencapsulation intermolecular details knowledge, essential in the definition of the parameters that controls the process. The work aimed to prepare biodegradable poly(hydroxybutyrate-hydroxyvalerate) (P(HB-HV)) microspheres through oil-in-water emulsion solvent evaporation technique, having controlled interaction with fluorescent probes. The study was conducted to evaluate how the polymer and some process parameters affect the final microspheres properties, such as polyvinyl alcohol (PVA) concentration, stirring speed emulsification, number of washing cycles during centrifugation, presence of the active compound to be encapsulated (coumarin, coumarin-6 and pyrene) and polymer molecular weight. The polymeric microspheres were evaluated by scanning electronic microscopy for their morphology analysis and size distribution; zeta-potential for their surface charge; confocal laser scanning microscopy for their encapsulation confirmation through coumarin-6 and pyrene localization; photophysics and release studies. From the results, it was found that the parameters most affected microsphere size were surfactant concentration (PVA) in the emulsion water phase, and the stirring speed of emulsification. Zeta-potential results were microsphere+pyrene< unloaded microsphere< microspheres+coumarin 6 in surface charge. Drug loadings (95% and 17%, m/m, to coumarin 6 and pyrene microparticles, respectively) indicated the occurrence of different interactions between polymer and fluorophore. Confocal fluorescence microscopy images confirmed the coumarin-6 aggregate formation inside the microsphere, while pyrene appeared as excimers in more external layers of the microparticles. Release behavior showed that the polymeric microspheres are polar and the coumarin-6 diffusion depends on the microparticles radius and the electrostatics interactions between polymer and fluorophore. Pyrene diffusion depends, only, on the hydrophobic interactions with the polymer / Doutorado / Físico-Química / Doutor em Quimica

Made available in DSpace on 2014-10-09T12:54:31Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:08:01Z (GMT). No. of bitstreams: 0 / A expansão do desenvolvimento de radionuclídeos para uso em terapia de tumores, permite que técnicas de tratamento de tumores sejam mais seletivas e adequadas. Novos agentes têm como finalidade reduzir o tempo de tratamento e acelerar o tempo de recuperação de muitos pacientes. O principal objetivo deste trabalho é o desenvolvimento de microesferas de ácido lático e resina marcadas com Hólmio-166, para que se obtenha um radiofármaco que possa oferecer um tratamento localizado do tumor e, portanto para que se tenha a máxima irradiação do tumor e a diminuição dos efeitos de toxicidade nos tecidos adjacentes saudáveis. A metástase hepática é a principal causa de morte de pacientes com câncer de colo retal, para estes pacientes a resposta da quimioterapia e da radioterapia é baixa. Uma alternativa é a radioterapia interna seletiva utilizando microesferas marcadas com Hólmio-166, um emissor b (Emax=1,84 MeV), com um alcance máximo no tecido de 8,4mm e emissor de fótons (81 keV, 6,2%), apropriado para a aquisição de imagens. A produção de Hólmio-166 é possível no reator nuclear IEA-R1 (IPEN-CNEN/SP), um reator de pesquisa com baixo fluxo de nêutrons. O Hólmio tem uma abundância de 100% na natureza e seção de choque de 64 barns. Isso permite produzir uma atividade de 344mCi (~12GBq) (reator IEA-R1, 60 horas, 4,0x 1013n .s-1.cm-2), o suficiente para produção de doses terapêuticas. As resinas de troca catiônica, AG50W-X2, AG50W-X8, Amberlite, Sephadex e Sepharose, foram marcadas com 166Ho. Todas elas apresentaram um ótimo resultado de marcação. As resinas AG50W-X2, AG50W-X8, Amberlite e Sephadex não têm o tamanho de partícula ideal para terapia de tumores hepáticos, porém foi proposto que partículas com tamanho entre 100-450 m podem ser usadas no tratamento de tumores de cabeça e pescoço. A resina Sepharose tem as características essenciais para terapia de tumores hepáticos. Entretanto, estudos in vivo devem ser realizados para comprovar a sua eficácia. O preparo das microesferas de ácido lático não foi bem sucedido, mas a primeira fase da preparação apresentou bons resultados. / Dissertação (Mestrado) / IPEN/D / Instituto de Pesquisas Energéticas e Nucleares - IPEN/CNEN-SP

Despite the great success of hip implant surgeries, wear particle-induced implant aseptic loosening still limits the implant longevity. Simvastatin, an FDA-approved cholesterol lowering statin, is a promising drug candidate for the treatment of implant aseptic loosening due to its anti-inflammatory properties as well as its ability to stimulate bone growth and inhibit bone resorption. In addition, alginate microspheres have been used extensively in drug delivery applications because of alginate properties, including biocompatibility and gelation in mild conditions. However, the hydrophobicity of simvastatin, as well as the large alginate microsphere pore size leading to the leakage of low molecular weight drugs are limiting factors for their use as a delivery system for simvastatin. Therefore, the objectives of this thesis were twofold: 1. To complex simvastatin with 2-hydroxypropyl-β-cyclodextrin (HP-βCD) in order to increase its solubility; and 2. To increase simvastatin encapsulation efficiency in alginate microspheres by coating the microspheres with chitosan, adding dextran sulfate in the alginate solution, and optimizing the gelation conditions used for the synthesis of the microspheres (e.g., volume of gelation medium, curing time, and addition of simvastatin in the gelation medium). Results showed that simvastatin complexation with HP-βCD increased with HP-βCD to simvastatin molar ratio, to a maximum of 97.6% at the molar ratio of 10. Results also showed that chitosan coating of the alginate microspheres increased simvastatin encapsulation efficiency (up to 10.6%), which was further improved (up to 14.0%) when adding 2.0% (w/v) dextran sulfate to the alginate solution. This increase was likely due to electrostatic interactions between dextran sulfate and chitosan in addition to alginate, resulting in a denser coating. Finally, the addition of simvastatin in the gelation medium was shown to also increase simvastatin encapsulation (up to 22.4%), likely because of a decrease in the diffusion of simvastatin out of the microspheres. Overall, this work completed the initial steps for the development of an alginate-based drug delivery system for simvastatin with the long-term goal of providing a local delivery of simvastatin to modulate implant aseptic loosening.

In the case of Parkinson’s disease, a common neurodegenerative disorder, the loss of motor function results from the selective degeneration of dopaminergic neurons (DNs) in the brain. Current treatments focus on pharmacological approaches that lose effectiveness over time and produce unwanted side effects. A more complete concept of rehabilitation to improve on current treatments requires the production of DNs to replace those that have been lost. Although pluripotent stem cells (PSCs) are a promising candidate for the source of these replacement neurons, current protocols for the terminal differentiation of DNs require a complicated cocktail of factors. Recently, a naturally occurring steroid called guggulsterone has been shown to be an effective terminal differentiator of DNs and can simplify the method for the production of such neurons. I therefore investigated the potential of long-term guggulsterone release from drug delivery particles in order to provide a proof of concept for producing DNs in a more economical and effective way. Throughout my study I was able to successfully encapsulate guggulsterone in Poly-ε-caprolactone (PCL)-based microspheres and I showed that the drug was capable of being released over 44 days in vitro. These guggulsterone-releasing microspheres were also successfully incorporated in human induced pluripotent stem cell (hiPSC)-derived neural aggregates (NAs), providing the foundation to continue investigating their effectiveness in producing functional and mature DNs. Together, these data suggest that guggulsterone delivery from microspheres may be a promising approach for improving the production of implantable DNs from hiPSCs. / Graduate