Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-12-29T16:13:13Z No. of bitstreams: 1 HenriqueRodriguesMarcelino_TESE.pdf: 41935029 bytes, checksum: f0753c6daecb5d46efe91996e88f61a5 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-01-02T16:17:22Z (GMT) No. of bitstreams: 1 HenriqueRodriguesMarcelino_TESE.pdf: 41935029 bytes, checksum: f0753c6daecb5d46efe91996e88f61a5 (MD5) / Made available in DSpace on 2017-01-02T16:17:23Z (GMT). No. of bitstreams: 1 HenriqueRodriguesMarcelino_TESE.pdf: 41935029 bytes, checksum: f0753c6daecb5d46efe91996e88f61a5 (MD5) Previous issue date: 2016-04-08 / Esta tese foi realizada com o objetivo geral de desenvolver e a caracterizar nanocarreadores com potencial para sobrepujar as propriedades biofarmac?uticas n?o-favor?veis da anfotericina B (AmB), uma mol?cula extremamente eficaz no tratamento de infec??es sistemicas fungicas e leishmaniose, mas dif?cil de formular independentemente da via de administra??o desejada. Acredita-se que essa mol?cula hidrof?bica possui limita??es devido a pronunciada tend?ncia de agregar sob condi??es fisiol?gicas humanas. A primeira parte desta tese foi conduzida pela hip?tese de que o estado de agrega??o da AmB teria um forte impacto sobre as propriedades farmacocin?ticas da mesma. Por tal raz?o, complexos de albumina e amB foram produzidos de forma a controlar o estado de agrega??o da AmB. A estrutura dos coloides obtidos foi caracterizada atrav?s de ensaios de espectroscopia UV-Vis e dicroismo circular. Adicionalmente, o impacto do estado de agrega??o na permeabilidade intestinal e no poss?vel reconhecimento dos agregados pelo sistema imunol?gico foram investigados. A segunda parte deste trabalho teve como objetivo o desenvolvimento de micro- e nanocarreadores para sobrepor as barreiras para absor??o da AmB ap?s a sua administra??o pela via oral. Para este fim, AmB foi incorporada em micro- e nanoemuls?es para observa??o da habilidade destes sistemas de incrementar a permeabilidade intestinal de mol?culas. Tal habilidade foi avaliada atrav?s do m?todo ex vivo de C?maras de Ussing, onde o tecido intestinal ? utilizado como barreira entre duas semi-c?maras. Nenhuma permea??o foi detectada nas condi??es experimentais utilizadas. No entanto, os dados obtidos atrav?s da medidas eletrofisiol?gicas demonstraram que a velocidade da perda da viabilidade do tecido ? dependente do estado de agrega??o da AmB em contato com o tecido. Tamb?m foi observado, atrav?s dos ensaios de permeabilidade que as rotas de absor??o paracelular e transcelular devem ser rotas marginais quando a absor??o da AmB ? observada in vivo, como descrito na literatura. Como alternativas, as rotas de absor??o pela captura de agregados e part?culas pelas placas de Peyer e a rota de absor??o linf?tica t?m sido discutidas. Finalmente, um otro sistema particulado que objetiva a libera??o em n?vel de col?n e baseada na utiliza??o da xilana, um biopol?mero natural e enzimaticamente degradado. A xilana ? polissacar?deo presente em gr?os, cereais e plantas angiospermas que ? especificamente degradado na regi?o col?nica, especificamente pela microbiota l? presente. A t?cnica aplicada de forma original consiste na forma??o de uma emuls?o ?gua-?gua de xilana em presen?a de PEG, seguida por uma etapa de reticula??o com o tris?dio trimetafosfato. Atrav?s da aplica??o desta t?cnica foi poss?vel produzir part?culas ? base de xilana que podem ter seu tamanho m?dio, de forma controlada, variado entre 380 nm e 4.5 ?m, de acordo com os par?metros utilizados. Esta t?cnica tamb?m ? livre do uso de solventes org?nicos e possui potencial aplica??o para a libera??o controlada de AmB em n?vel de col?n. / This thesis is part of the development and evaluation of nanomedicines potentially able to overcome unfavorable biopharmaceutical properties of amphotericin B (AmB), a highly effective molecule used for the treatment of systemic fungal infections and leishmaniasis, but difficult to formulate efficiently, whatever the route of delivery. It is believed that this hydrophobic molecule suffers from severe limitations due to its pronounced tendency to aggregate under physiological conditions. The first part of the thesis was driven on the hypothesis that the degree of aggregation of AmB could have a strong impact on some of its pharmacokinetics properties. For this purpose albumin has been used to produce controlled complexes between albumin and AmB in order to control AmB aggregation states. The morphological characteristics of the resulting colloidal objects have been carefully characterized by UV-Vis spectroscopy and circular dichroism. Furthermore, the impact of aggregation state on both the intestinal permeability and a possibly expected recognition of the aggregates by the immunological system were investigated. The second part of this work was focused on the development of micro- and nanocarriers intended to overcome the absorption barrier raised against AmB after oral delivery. For this purpose, AmB was loaded into micro- and nanoemulsions to evaluate a possible permeability enhancement effect through the intestinal membrane, which was evaluated in ratas using the Ussing chamber model. No detectable permeation was seen in any of the experimental conditions. However, the electrophysiological data showed tissue viability losses due to the strong toxicity of AmB, that were dependent on the aggregation state of AmB when in contact with the tissue. It was also concluded from detailed permeation experiments in healthy tissues that paracellular and transcellular routes were likely to be only marginal pathways when oral absorption are observed in vivo, as reported in the literature. The likeness of other possible absorption pathways, including Peyer's patches capture and lymphatic pathway implication for aggregated particles has been discussed. Finally, another particulate system intended for colonic delivery and based on xylan, a natural and enzymatically degradable biopolymer, has been investigated. Xylan is a polysaccharide present in grains, cereals and angiosperm plants that is specifically degraded on colon region, by the microbiota. An original process consisting in a water-in-water emulsion of xylan in presence of PEG followed by a crosslinking phase using trisodium trimetaphosphate has been developed, making possible the production of xylan-based biocompatible micro- and nanospheres ranging from 380 nm to 4.5 ?m, depending on the parameters in the process. This eco-friendly process is free of harmful solvents and has potential application for the delivery of AmB at the colonic level.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-04-04T18:40:22Z No. of bitstreams: 1 CamillaCarlaDoNascimentoDantasCardoso_DISSERT.pdf: 1584071 bytes, checksum: f40f4e02e45ed4aae3bbf022f745a170 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-04-12T21:48:51Z (GMT) No. of bitstreams: 1 CamillaCarlaDoNascimentoDantasCardoso_DISSERT.pdf: 1584071 bytes, checksum: f40f4e02e45ed4aae3bbf022f745a170 (MD5) / Made available in DSpace on 2017-04-12T21:48:51Z (GMT). No. of bitstreams: 1 CamillaCarlaDoNascimentoDantasCardoso_DISSERT.pdf: 1584071 bytes, checksum: f40f4e02e45ed4aae3bbf022f745a170 (MD5) Previous issue date: 2016-12-12 / A doen?a inflamat?ria intestinal (DII) engloba um espectro de dist?rbios inflamat?rios cr?nicos e ? classificada em dois subtipos principais: Colite Ulcerativa (UC) e Doen?a de Chron (DC). O tratamento da UC baseia-se no uso de anti-inflamat?rios, mas estes medicamentos na sua forma convencional geram in?meros efeitos adversos, o que estimula o desenvolvimento de pesquisas focadas na busca por novas terapias e tecnologias aplicadas aos f?rmacos. O objetivo deste trabalho foi avaliar a atividade de micropart?culas revestidas por Biopol?meros de quitosana e goma guar contendo como princ?pio ativo a triancinolona, no intuito de observar a resposta anti-inflamat?ria nos par?metros macro e microsc?picos da mucosa intestinal. Foram utilizados 56 ratos Wistar, divididos em 08 grupos de 7 animais, sendo G1: Controle negativo (aus?ncia de colite), G2: Colite, G3: Sulfassalazina (SSZ 500mg/Kg/dia), G4: Triancinolona (TR) livre 5mg/Kg/dia, G5: TR livre 10mg/Kg/dia, G6: TR livre 15mg/Kg/dia, G7: Micropart?cula de TR (15mg/Kg/dia f?rmaco encapsulado) e o grupo G8: Biopol?meros. Os resultados obtidos quanto ao par?metro de avalia??o macrosc?pica mostraram que o menor grau de les?o, com exce??o do grupo Controle negativo, foi encontrado no grupo dos Biopol?meros e SSZ quando comparado aos demais grupos: Colite, TR 5mg, TR 10mg, TR 15mg e Micropart?cula TR. Na an?lise estat?stica desse par?metro os grupos SSZ 500mg/Kg/dia, TR 15mg/kg/dia, Micropart?cula TR 15mg/Kg/dia e Biopol?meros diferiram estatisticamente quando comparadas ao grupo Colite (p<0,05), sendo esta diferen?a mais significativa no grupo dos Biopol?meros (p<0,01). Na an?lise da perda de peso, o grupo Micropart?cula TR reduziu entre 8 a 12% esse par?metro quando comparado aos grupos da Triancinolona livre, diferindo estatisticamente (p<0,05), evidenciando que a tecnologia empregada foi satisfat?ria quanto a redu??o desse efeito adverso. Na avalia??o histopatol?gica o grupo TR 15mg/kg/dia obteve o menor dano tissular, evidenciando o potencial anti-inflamat?rio do f?rmaco livre. Diante dos resultados sugere-se que a nanotecnologia com o uso das micropart?culas foi capaz de reduzir efeitos adversos, como a perda de peso e, al?m disso, obteve resultados com potencial efeito anti-inflamat?rio, apesar da libera??o de apenas 69% dos 15mg da triancinolona encapsulada em 24 horas. Assim, os estudos voltados para aplica??o da nanotecnologia e novos ativos devem crescer e ampliar com intuito de buscar novas terapias e elucidar mecanismos de a??o ainda n?o descobertos. / The inflammatory bowel disease (IBD) encompasses a spectrum of chronic inflammatory disorders and is classified into two main subtypes: Ulcerative Colitis (UC) and Chron's Disease (CD). The treatment of UC is based on the use of anti-inflammatories, but these drugs in their conventional form generate numerous adverse effects, which stimulates the development of research focused on the search for new therapies and technologies applied to the drugs. The objective of this study was to evaluate the activity of microparticles coated by chitosan and guar gum biopolymers containing as active principle triamcinolone in intention to observe the anti-inflammatory response in the macroscopic and microscopic parameters of the intestinal mucosa. In total, 56 Wistar rats divided into 8 groups in 7 animals, being G1: Negative control (absence of colitis), G2: Colitis, G3: Sulfasalazine (SSZ 500mg/Kg/day), G4: Free triamcinolone (TR) 5mg/Kg/day, G5: Free TR 10mg/Kg/day, G6: Free TR 15mg/Kg/day, G7: Triamcinolone microparticle (15mg/Kg/day), G8: Biopolymers. The results obtained for the macroscopic evaluation showed that the lowest lesion degree, except for the negative control group, was found in the Biopolymer group and SSZ group when compared to the other groups: Colitis, TR 5mg, TR 10mg, TR 15mg and TR microparticle. In the statistical analysis of this parameter, the groups treated with SSZ 500mg/kg/day, TR 15mg/kg/day, TR microparticle 15mg/Kg/day and Biopolymers differed statistically when compared to the Colitis group (p<0.05), this difference being more significant in the Biopolymer group (p<0.01). In the analysis of weight loss, the TR microparticle reduced this parameter between 8 and 12% when compared to the free Triamcinolone groups, differing statistically (p<0.05), suggesting that the technology employed was satisfactory in terms of the reduction of this adverse effect. In the histopathological evaluation, the TR group 15mg/kg/day obtained the lowest tissue damage, evidencing the anti-inflammatory potential of the free drug. In view of the results, it is suggested that nanotechnology with the use of microparticles was able to reduce adverse effects, such as weight loss and, in addition, obtained results with a potential anti-inflammatory effect, despite the release of only 69% of 15mg of encapsulated triamcinolone in 24 hours. Thus, studies aimed at the application of nanotechnology and new assets should grow and expand in order to seek new therapies and elucidate mechanisms of action that have not yet been discovered.

Made available in DSpace on 2014-12-17T14:16:37Z (GMT). No. of bitstreams: 1 EdileneGO_DISSERT.pdf: 1950686 bytes, checksum: 88f16924cd116b850ade306c274f71ac (MD5) Previous issue date: 2014-12-20 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / New drug delivery systems have been used to increase chemotherapy efficacy due the possible drug resistance of cancer cells. Poly (lactic acid) (PLA) microparticles are able to reduce toxicity and prolong methotrexate (MTX) release. In addition, the use of PLA/poloxamer polymer blends can improve drug release due to changes in the interaction of particles with biological surfaces. The aim of this study was developing spray dried biodegradable MTX-loaded microparticles and evaluate PLA interactions with different kinds of Pluronic? (PLUF127 and PLUF68) in order to modulate drug release. The variables included different drug:polymer (1:10, 1:4.5, 1:3) and polymer:copolymer ratios (25:75, 50:50, 75:25). The precision and accuracy of spray drying method was confirmed assessing drug loading into particles (75.0- 101.3%). The MTX/PLA microparticles showed spherical shape with an apparently smooth surface, which was dependent on the PLU ratio used into blends particles. XRD and thermal analysis demonstrated that the drug was homogeneously dispersed into polymer matrix, whereas the miscibility among components was dependent on the used polymer:copolymer ratio. No new drug- polymer bond was identified by FTIR analysis. The in vitro performance of MTX-loaded PLA microparticles demonstrated an extended-release profile fitted using Korsmeyer- Peppas kinetic model. The PLU accelerated drug release rate possible due PLU leached in the matrix. Nevertheless, drug release studies carried out in cell culture demonstrated the ability of PLU modulating drug release from blend microparticles. This effect was confirmed by cytotoxicity observed according to the amount of drug released as a function of time. Thus, studied PLU was able to improve the performance of spray dried MTX-loaded PLA microparticles, which can be successfully used as carries for modulated drug delivery with potential in vivo application / Novos sistemas de libera??o de f?rmacos v?m sendo utilizados para aumentar a efic?cia de quimioter?picos devido ? poss?vel resist?ncia de c?lulas cancer?genas. As micropart?culas de poli (?cido l?ctico) (PLA) constituem uma alternativa para diminuir a toxicidade e prolongar a libera??o do metotrexato (MTX). Al?m disso, o uso de blendas polim?ricas PLA-polox?meros pode melhorar o perfil de libera??o do f?rmaco devido a mudan?as nas intera??es das part?culas com superf?cies biol?gicas. O objetivo do estudo foi desenvolver micropart?culas biodegrad?veis de MTX produzidas por spray drying e avaliar intera??es PLA-Pluronic? (PLA-PLU) para modular a libera??o do f?rmaco, utilizando diferentes tipos de Pluronic? (PLUF127 e PLUF68). As vari?veis de composi??o inclu?ram raz?es f?rmaco:pol?mero (1:10; 1:4,5; 1:3) e pol?mero:copol?mero (25:75, 50:50, 75:25). A reprodutibilidade e a efic?cia do m?todo de produ??o foram confirmadas pela alta efici?ncia de incorpora??o dos sistemas (75,0-101,3%). As micropart?culas de MTX/PLA apresentaram-se esf?ricas com superf?cie aparentemente lisa. Este formato mostrou-se dependente da raz?o pol?mero:copol?mero nas part?culas contendo blendas. A an?lise t?rmica e a difra??o de raios-X sugerem que h? dispers?o do f?rmaco por toda a matriz, enquanto que a miscibilidade entre os componentes foi dependente da raz?o pol?mero:copol?mero. Nenhuma liga??o qu?mica entre o f?rmaco e o pol?mero foi identificada pela an?lise de FTIR. As micropart?culas de PLA contendo MTX apresentaram perfil de libera??o prolongada com um prevalente modelo cin?tico de Korsmeyer-Peppas. O PLU acelerou a taxa de libera??o do f?rmaco devido a sua poss?vel sa?da da matriz polim?rica. Por outro lado, estudos de libera??o do f?rmaco realizados em cultura de c?lulas demonstraram que o PLU modula a taxa de MTX liberado a partir de micropart?culas contendo blendas. Este efeito foi confirmado pela citotoxicidade dos sistemas estudados, de acordo com a quantidade de f?rmaco liberado em fun??o do tempo. Portanto, o uso de PLU foi capaz de melhorar o perfil de libera??o de micropart?culas de PLA contendo MTX, o qual pode ser utilizado como carreador para modular a libera??o do f?rmaco com potencial aplica??o in vivo

Made available in DSpace on 2014-12-17T14:13:48Z (GMT). No. of bitstreams: 1 AcariliaES_TESE.pdf: 9221805 bytes, checksum: 71876e327362584aeb9dcac7d3652c4d (MD5) Previous issue date: 2013-04-05 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / This thesis was devoted to the development of innovative oral delivery systems for two different molecules. In the first part, microparticles (MPs) based on xylan and Eudragit? S- 100 were produced and used to encapsulate 5-aminosalicylic acid for colon delivery. Xylan was extracted from corn cobs and characterized in terms of its physicochemical, rheological and toxicological properties. The polymeric MPs were prepared by interfacial cross-linking polymerization and spray-drying and characterized for their morphology, mean size and distribution, thermal stability, crystallinity, entrapment efficiency and in vitro drug release. MPs with suitable physical characteristics and satisfactory yields were prepared by both methods, although the spray-dried systems showed higher thermal stability. In general, spraydried MPs would be preferable systems due to their thermal stability and absence of toxic agents used in their preparation. However, drug loading and release need to be optimized. In the second part of this thesis, oil-in-water microemulsions (O/W MEs) based on mediumchain triglycerides were formulated as drug carriers and solubility enhancers for amphotericin B (AmB). Phase diagrams were constructed using surfactant blends with hydrophiliclipophilic balance values between 9.7 and 14.4. The drug-free and drug-loaded MEs presented spherical non-aggregated droplets around 80 and 120 nm, respectively, and a low polydispersity index. The incorporation of AmB was high and depended on the volume fraction of the disperse phase. These MEs did not reduce the viability of J774.A1 macrophage-like cells for concentrations up to 25 &#956;g/mL of AmB. Therefore, O/W MEs based on propylene glycol esters of caprylic acid may be considered as suitable delivery systems for AmB / Esta tese teve como objetivo o desenvolvimento de novos sistemas de libera??o para duas mol?culas distintas. Na primeira parte, micropart?culas ? base de xilana e Eudragit? S-100 foram produzidas para encapsular ?cido 5-aminosalic?lico visando ? libera??o c?lonespec?fica. A xilana foi extra?da de sabugos de milho e caracterizada quanto ?s suas propriedades f?sico-qu?micas, reol?gicas e toxicol?gicas. Em seguida, dois m?todos de microencapsula??o foram utilizados: reticula??o interfacial polim?rica e secagem por aspers?o. Os sistemas produzidos foram caracterizados quanto ? morfologia, tamanho m?dio e distribui??o, estabilidade t?rmica, cristalinidade, taxa de encapsula??o e libera??o do f?rmaco in vitro. Foram obtidas micropart?culas com adequadas caracter?sticas f?sicas e rendimentos satisfat?rios atrav?s dos dois m?todos, embora os sistemas aspergidos tenham apresentado maior estabilidade t?rmica e sejam considerados mais interessantes devido a sua maior estabilidade t?rmica e aus?ncia de agentes t?xicos. No entanto, ajustes precisam ser feitos para melhorar a encapsula??o e libera??o do f?rmaco. Na segunda parte, microemuls?es do tipo ?leo em ?gua (MEs O/A) com base em triglicer?deos de cadeia m?dia (MCT) foram produzidas visando ao carreamento de anfotericina B (AmB) e aumento da sua solubilidade. Foram obtidas MEs O/A sem e com AmB com got?culas em torno de 80 e 120 nm, respectivamente, e ?ndices de polidispers?o de 0,25 e 0,31, respectivamente. A taxa de incorpora??o da AmB foi alta e dependente do volume da fase dispersa. A viabilidade celular n?o foi afetada at? 25 &#956;g/mL da AmB. Portanto, MEs O/A a partir de MCT podem ser promissores sistemas de libera??o para AmB

Made available in DSpace on 2014-12-17T14:16:27Z (GMT). No. of bitstreams: 1 AliceRO_DISSERT.pdf: 2104659 bytes, checksum: 208850f5293dd4764037ec4c490d3636 (MD5) Previous issue date: 2011-12-19 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Methotrexate (MTX) is a drug used in the chemotherapy of some kind of cancers, autoimmune diseases and non inflammatory resistant to corticosteroids uveits. However, the rapid plasmatic elimination limits its therapeutic success, which leads to administration of high doses to maintain the therapeutic levels in the target tissues, occurring potential side effects. The aim of this study was to obtain spray dried biodegradable poly-lactic acid co-glycolic acid (PLGA) microparticles containing MTX. Thus, suitable amounts of MTX and PLGA were dissolved in appropriate solvent system to obtain solutions at different ratios drug/polymer (10, 20, 30 and 50% m/m). The physicochemical characterizing included the quantitative analysis of the drug using a validate UV-VIS spectrophotometry method, scanning electron microscopy (SEM), infrared spectrophotometry (IR), thermal analyses and X-ray diffraction analysis. The in vitro release studies were carried out in a thermostatized phosphate buffer pH 7.4 (0.05 M KH2PO4) medium at 37?C ? 0.2 ?C. The in vitro release date was subjected to different kinetics release models. The MTX-loaded PLGA microparticles showed a spherical shape with smooth surface and high level of entrapped drug. The encapsulation efficiency was greater then 80%. IR spectroscopy showed that there was no chemical bond between the compounds, suggesting just the possible occurrence of hydrogen bound interactions. The thermal analyses and X-ray diffraction analysis shown that MTX is homogeneously dispersed inside polymeric matrix, with a prevalent amorphous state or in a stable molecular dispersion. The in vitro release studies confirmed the sustained release for distinct MTX-loaded PLGA microparticles. The involved drug release mechanism was non Fickian diffusion, which was confirmed by Kornmeyer-Peppas kinetic model. The experimental results demonstrated that the MTX-loaded PLGA microparticles were successfully obtained by spray drying and its potential as prolonged drug release system. / O metotrexato (MTX) ? um f?rmaco utilizado na quimioterapia de alguns tipos de c?ncer, doen?as autoimunes e uve?tes n?o inflamat?rias resistentes aos corticoster?ides. No entanto, sua r?pida elimina??o plasm?tica limita o sucesso terap?utico, levando ? necessidade de altas doses para manuten??o da concentra??o efetiva no tecido alvo, ocasionando o potencial surgimento de rea??es adversas. O objetivo principal desse estudo foi obter um sistema microparticulado biodegrad?vel ? base de ?cido poli (?cido l?tico-co-?cido glic?lico) (PLGA) por spray drying para libera??o prolongada do MTX. Para isso, quantidades distintas de MTX e PLGA foram dissolvidas em sistema solvente adequado para obter solu??es com diferentes propor??es de f?rmaco em rela??o ao pol?mero (10, 20, 30 e 50% m/m). A caracteriza??o f?sicoqu?mica incluiu an?lise quantitativa do f?rmaco incorporado na matriz polim?rica por espectrofotometria UV-VIS em 303nm previamente validada, microscopia eletr?nica de varredura (MEV), espectrofotometria de infravermelho (IV), an?lises t?rmicas e difra??o de raios-X (DRX). O perfil de libera??o in vitro do f?rmaco nas micropart?culas foi realizado em tamp?o fosfato (0.05 M KH2PO4) em banho termostatizado 37 ?C ? 0.2 ?C. Os dados obtidos do estudo de libera??o in vitro foram submetidos a diferentes modelos cin?ticos de libera??o. As micropart?culas de PLGA contendo o MTX apresentaram a forma esf?rica, uniforme, com superf?cie aparentemente lisa. O n?vel de efici?ncia de encapsula??o foi superior a 80%. A espectroscopia na regi?o do infravermelho demonstrou que n?o ocorreu liga??o qu?mica entre os componentes dos sistemas, no entanto foi observado forte intera??o entre o MTX e PLGA indicando prov?vel ocorr?ncia de pontes de hidrog?nio. An?lise XII t?rmica e DRX demonstraram que o MTX est? distribu?do na matriz polim?rica com a preval?ncia do estado amorfo ou em dispers?o molecular. O estudo de libera??o in vitro confirmou o perfil de libera??o prolongada para as diferentes micropart?culas. O mecanismo de libera??o envolvido foi por difus?o n?o Fickiana, ao qual foi determinado a partir do modelo cin?tico de Kornmeyer- Peppas. Os resultados experimentais demonstraram o sucesso na obten??o das micropart?culas de PLGA contendo o MTX por spray drying e seu potencial como sistema de libera??o prolongada do f?rmaco.

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 40&#956;m. 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 40&#956;m, 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