Made available in DSpace on 2014-12-17T14:13:45Z (GMT). No. of bitstreams: 1 SilvaEL_DISSERT.pdf: 2857936 bytes, checksum: 9a0ed46e2b6c06e351eff5810e5f24d8 (MD5) Previous issue date: 2010-03-31 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Magnetic targeting is being investigated as a means of local delivery of drugs, combining precision, minimal surgical intervention, and satisfactory concentration of the drug in the target region. In view of these advantages, it is a promising strategy for improving the pharmacological response. Magnetic particles are attracted by a magnetic field gradient, and drugs bound to them can be driven to their site of action by means of the selective application of magnetic field on the desired area. Helicobacter pylori is the commonest chronic bacterial infection. The treatment of choice has commonly been based upon a triple therapy combining two antibiotics and an anti-secretory agent. Furthermore, an extended-release profile is of utmost importance for these formulations. The aim of this work was to develop a magnetic system containing the antibiotic amoxicillin for oral magnetic drug targeting. First, magnetic particles were produced by coprecipitation of iron salts in alkaline medium. The second step was coating the particles and amoxicillin with Eudragit? S-100 by spray-drying technique. The system obtained demonstrated through the characterization studies carried out a possible oral drug delivery system, consisting in magnetite microparticles and amoxicillin, coated with a polymer acid resistant. This system can be used to deliver drugs to the stomach for treatment of infections in this organ. Another important finding in this work is that it opens new prospects to coat magnetic microparticles by the technique of spray-drying. / A vetoriza??o magn?tica tem sido investigada como uma forma de entrega local de f?rmacos combinando precis?o, m?nima interven??o cir?rgica e concentra??o satisfat?ria do f?rmaco na regi?o de interesse. Part?culas magn?ticas s?o atra?das a partir da aplica??o de um campo magn?tico e f?rmacos associados a essas part?culas podem ser direcionados ao seu s?tio de a??o atrav?s de uma aplica??o seletiva do campo na regi?o de interesse. Helicobacter pylori ? a mais comum causa de infec??o bacteriana cr?nica no est?mago. O tratamento padr?o ? a tripla terapia oral contendo dois antibi?ticos e um inibidor da bomba de pr?tons. Sendo assim, um perfil de libera??o prolongada ? de suma import?ncia para essas formula??es. O objetivo deste trabalho foi desenvolver um sistema magn?tico com potencial emprego na vetoriza??o de antibi?tico por via oral. Inicialmente, part?culas magn?ticas foram produzidas por co-precipita??o de sais de ferro em meio alcalino. Em seguida, as part?culas foram revestidas a partir da dispers?o da suspens?o magn?tica em uma solu??o contendo o pol?mero dissolvido e a amoxicilina, e ent?o submetido ? secagem por aspers?o (spray-drying). Atrav?s das caracteriza??es realizadas p?de-se verificar a obten??o de um potencial sistema para vetoriza??o de f?rmacos por via oral contendo micropart?culas de magnetita e amoxicilina revestidos por um pol?mero gastro-resistente. Adicionalmente, um importante aspecto nesse trabalho ? a abertura de novas perspectivas para o revestimento de micropart?culas magn?ticas atrav?s da t?cnica de spray-drying.

Made available in DSpace on 2015-02-24T17:42:52Z (GMT). No. of bitstreams: 1 ThalesRFP_DISSERT.pdf: 5363462 bytes, checksum: 16f2d3a123870a2d8c63de00ac4bf689 (MD5) Previous issue date: 2014-02-24 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Helicobacter pylori is the main cause of gastritis, gastroduodenal ulcer disease and gastric cancer. The most recommended treatment for eradication of this bacteria often leads to side effects and patient poor compliance, which induce treatment failure. Magnetic drug targeting is a very efficient method that overcomes these drawbacks through association of the drug with a magnetic compound. Such approach may allow such systems to be placed slowed down to a specific target area by an external magnetic field. This work reports a study of the synthesis and characterization of polymeric magnetic particles loaded with the currently used antimicrobial agents for the treatment of Helicobacter pylori infections, aiming the production of magnetic drug delivery system by oral route. Optical microscopy, scanning electron microscopy, transmission electron microscopy, x-ray powder diffraction, nitrogen adsorption/desorption isotherms and vibrating sample magnetometry revealed that the magnetite particles, produced by the co-precipitation method, consisted of a large number of aggregated nanometer-size crystallites (about 6 nm), creating superparamagnetic micrometer with high magnetic susceptibility particles with an average diameter of 6.8 ? 0.2 μm. Also, the polymeric magnetic particles produced by spray drying had a core-shell structure based on magnetite microparticles, amoxicillin and clarithromycin and coated with Eudragit? S100. The system presented an average diameter of 14.2 ? 0.2 μm. The amount of magnetite present in the system may be tailored by suitably controlling the suspension used to feed the spray dryer. In the present work it was 2.9% (w/w). The magnetic system produced may prove to be very promising for eradication of Helicobacter pylori infections / A Helicobacter pylori ? a principal causa de gastrites, ?lceras gastroduodenais e c?ncer g?strico. O esquema terap?utico de primeira escolha para a erradica??o desse pat?geno leva muitas vezes a elevado n?mero de rea??es adversas, baixa ades?o do paciente e consequentemente falha na terap?utica. A vetoriza??o magn?tica ? uma t?cnica bastante difundida na literatura que visa minimizar esses problemas, atrav?s da associa??o de f?rmacos a n?cleos magn?ticos direcionando para o local de a??o por interm?dio de campo magn?tico externo. O presente trabalho relata o estudo da s?ntese e caracteriza??o de part?culas polim?ricas magn?ticas contendo os mais frequentes antimicrobianos (amoxicilina e claritromicina) usados no tratamento de infec??es por Helicobacter pylori, objetivando a produ??o de um sistema para vetoriza??o magn?tica por via oral. Granulometria baseada no di?metro de Feret, microscopia eletr?nica de varredura e transmiss?o, difratometria de raio-x, isotermas de adsor??o/dessor??o de nitrog?nio e magnetometria de amostra vibrante revelaram que as part?culas de magnetita, produzidas pelo m?todo da coprecipita??o, consistem em grande n?mero de agregados de cristalitos de tamanhos nanom?tricos (da ordem de 6 nm) os quais formam part?culas microm?tricas superparamagn?ticas de alta susceptibilidade magn?tica, tendo formato irregular com di?metro m?dio de 6,8 ? 0,2 μm. Os n?cleos magn?ticos foram revestidos por pol?mero (Eudragit? S100) em conjunto com amoxicilina e claritromicina (forma polim?rfica II) sendo obtido micropart?culas n?cleo-camada de formato irregular, pela t?cnica de secagem por aspers?o (spray dryer), com um di?metro m?dio de 14,2 ? 0,2 μm. A quantidade de magnetita presente no sistema pode ser adaptada pelo controle da suspens?o inicial usada na alimenta??o do spray dryer. No presente trabalho o conte?do magn?tico final foi estimado em 2,9 % (p/p). Com base nos resultados obtidos, o sistema magn?tico produzido pode se tornar bastante promissor na erradica??o de infec??es por Helicobacter pylori

Made available in DSpace on 2014-12-17T14:16:25Z (GMT). No. of bitstreams: 1 AcariliaES_Dissert_01.pdf: 1640327 bytes, checksum: 9c4568aff953d538d26000691eb0407d (MD5) Previous issue date: 2009-03-10 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Colon-specific drug delivery systems have attracted increasing attention from the pharmaceutical industry due to their ability of treating intestinal bowel diseases (IBD), which represent a public health problem in several countries. In spite of being considered a quite effective molecule for the treatment of IBD, mesalazine (5-ASA) is rapidly absorbed in the upper gastrointestinal tract and its systemic absorption leads to risks of adverse effects. The aim of this work was to develop a microparticulate system based on xylan and Eudragit? S- 100 (ES100) for colon-specific delivery of 5-ASA and evaluate the interaction between the polymers present in the systems. Additionaly, the physicochemical and rheological properties of xylan were also evaluated. Initially, xylan was extracted from corn cobs and characterized regarding the yield and rheological properties. Afterwards, 10 formulations were prepared in different xylan and ES100 weight ratios by spray-drying the polymer solutions in 0.6N NaOH and phosphate buffer pH 7.4. In addition, 3 formulations consisting of xylan microcapsules were produced by interfacial cross-linking polymerization and coated by ES100 by means of spray-drying in different polymer weight ratios of xylan and ES100. The microparticles were characterized regarding yield, morphology, homogeneity, visual aspect, crystallinity and thermal behavior. The polymer interaction was investigated by infrared spectroscopy. The extracted xylan was presented as a very fine and yellowish powder, with mean particle size smaller than 40μm. Regarding the rheological properties of xylan, they demonstrated that this polymer has a poor flow, low density and high cohesiveness. The microparticles obtained were shown to be spherical and aggregates could not be observed. They were found to present amorphous structure and have a very high thermal stability. The yield varied according to the polymer ratios. Moreover, it was confirmed that the interaction between xylan and ES100 occurs only by means of physical aggregation / Sistemas c?lon-espec?ficos t?m atra?do o interesse da ind?stria farmac?utica devido ? possibilidade de tratarem enfermidades, como as doen?as inflamat?rias intestinais (DII), que compreendem um problema de sa?de p?blica em muitos pa?ses. Apesar de ser considerada uma mol?cula bastante eficiente para o tratamento das DII, a mesalazina (5-ASA) ? rapidamente absorvida no trato gastrintestinal superior e sua absor??o sist?mica leva ? incid?ncia de s?rios efeitos adversos. Este trabalho teve como objetivos produzir um sistema polim?rico microparticulado ? base de xilana e Eudragit? S-100 (ES100) para libera??o c?lon-espec?fica de 5-ASA e avaliar a intera??o entre os pol?meros constituintes do sistema, al?m de aprofundar a caracteriza??o f?sico-qu?mica e tecnol?gica da xilana. A xilana foi extra?da a partir de sabugos de milho e caracterizada quanto ao rendimento, granulometria, cristalinidade, propriedades reol?gicas e comportamento t?rmico. Em seguida, 10 formula??es contendo 5-ASA foram preparadas em diferentes propor??es de xilana e ES100 atrav?s da secagem por aspers?o das solu??es polim?ricas com NaOH 0,6N ou tamp?o-fosfato pH 7,4, como solvente. Al?m disso, 3 formula??es constitu?das de microc?psulas de xilana produzidas por reticula??o polim?rica interfacial foram revestidas por ES100 atrav?s de secagem por aspers?o em diferentes propor??es polim?ricas e empregando-se NaOH 0,6N ou tamp?o-fosfato pH 7,4, como solvente. As micropart?culas foram avaliadas quanto ao rendimento, morfologia, granulometria, homogeneidade, aspecto visual, cristalinidade e comportamento t?rmico. A intera??o entre os pol?meros foi investigada atrav?s da espectroscopia na regi?o do infravermelho e de an?lises t?rmicas. A xilana extra?da apresentou-se como um p? muito fino, com tamanho m?dio inferior a 40μm, e com colora??o opaca levemente amarelada. A avalia??o das propriedades reol?gicas da xilana permitiram a caracteriza??o desse pol?mero, em seu estado original de p?, como um material de baixa densidade, fluxo restrito e bastante coesivo. Foram obtidas micropart?culas esf?ricas e sem presen?a de agregados, com estrutura amorfa, em sua maior parte, e bastate est?veis a temperaturas elevadas. Al?m disso, confirmou-se que a intera??o entre xilana e ES100 ocorre apenas por agrega??o f?sica