Stable single-unit recordings from the nervous system using microelectrode arrays can have significant implications for the treatment of a wide variety of sensory and movement disorders. However, the long-term performance of the implanted neural electrodes is compromised by the formation of glial scar around these devices, which is a typical consequence of the inflammatory tissue reaction to implantation-induced injury in the CNS. The glial scar is inhibitory to neurons and forms a barrier between the electrode and neurons in the surrounding brain tissue. Therefore, to maintain long-term recording stability, reactive gliosis and other inflammatory processes around the electrode need to be minimized. This work has succeeded in the development of neural electrode coatings that are capable of sustained release of anti-inflammatory agents while not adversely affecting the electrical performance of the electrodes. The effects of coating methods, initial drug loadings on release kinetics were investigated to optimize the coatings. The physical properties of the coatings and the bioactivity of released anti-inflammatory agents were characterized. The effect of the coatings on the electrical property of the electrodes was tested. Two candidate anti-inflammatory agents were screened by evaluating their anti-inflammatory potency in vitro. Finally, neural electrodes coated with the anti-inflammatory coatings were implanted into rat brains to assess the anti-inflammatory potential of the coatings in vivo. This work represents a promising approach to attenuate astroglial scar around the implanted silicon neural electrodes, and may provide a promising strategy to improve the long-term recording stability of silicon neural electrodes.

Zeolites have been used in agriculture since the 1960s, due to the effectiveness of these crystalline microporous solids as soil amendments for plant growth, their cation exchange capacity (CEC) and slow-release fertilizer properties. Most work on slow-release fertilizers has focused on natural Clinoptilolite, Phillipsite and Chabazite. The aim of this study was to synthesize zeolites, study their effectiveness as soil amendments and their ability to act as controlled release fertilizers to decrease nitrate leaching. Nitrate pollution of groundwater is a major agro-environmental concern. The zeolites Phillipsite and Linde-type F were synthesized from aluminosilicate gels; ion exchanged to introduce ammonium and characterized using X-ray diffraction (XRD), X-ray fluorescence (XRF), Thermo-gravimetric analysis (TGA) and Scanning electron microscopy (SEM) techniques, both before and after ion exchange. Ammoniumexchanged Phillipsites (natural and synthetic), ammonium-exchanged synthetic Linde-type F (the zeolite having highest affinity towards ammonium) and ammonium exchanged Phillipsites (high crystalline and high aluminium) were compared with conventional NPK fertilizer.Three glasshouse experiments were performed to study the effects of zeolite-amended soils on maize growth. Ion exchanged synthetic and natural Phillipsites were first used as soil amendments (w/w 2, 4, 8% zeolite to soil). Synthetic Phillipsite, at 2% loading, resulted in the most significant improvement in both plant growth and phased ammonium release. The synthetic ammonium-exchanged zeolites Phillipsite and Linde-type F (at w/w 1, 2, 4%) were then compared; synthetic Phillipsite, at 2% loading, again resulted in the most significant plant growth response with an increase (≥15%) in shoot dry weight and a decrease (≥30%) in nitrate leaching. Experiments using unexchanged synthetic Phillipsite (at w/w 2%), but with added NPK fertilizer, showed increased plant growth and decreased nitrate leaching, compared with parallel experiments containing unexchanged synthetic Linde-type F (at w/w 2%) and a conventional fertilizer amended soil. This revealed the beneficial effect of Phillipsite for soil amendment, even without ion exchange to the ammonium form. To study the physico-chemical properties affecting the release of ammonium from the Phillipsite framework; high crystalline/low aluminium and low crystalline/high aluminium forms were synthesized and ion exchanged. Both forms were introduced as soil amendments (at w/w 1 and 2%) and experiments showed that the lower zeolite crystallinity decreased cation exchange and therefore decreased nitrate leaching. Experimental results from the glasshouse experiments and cation exchange capacity (CEC) experiments suggest that synthetic Phillipsite, at lower loadings (1 and 2% w/w zeolite to soil) have most potential as soil amendments for both plant growth and controlled-release applications. This conclusion is supported by soil leachate and shoots dry weight analysis. Furthermore, Phillipsite, synthesized in a low crystalline and low ammonium form, may be an even better soil amendment for controlled release of ammonium, which will thereby further decrease nitrate pollution.

Submitted by Johnny Rodrigues (johnnyrodrigues@ufcg.edu.br) on 2018-04-11T15:06:17Z No. of bitstreams: 1 LEONARDO FALCÃO FEITOSA - DISSERTAÇÃO PPG-CEMat 2014..pdf: 2258061 bytes, checksum: cdc233909fd365937aacd1ef5fa7c2cd (MD5) / Made available in DSpace on 2018-04-11T15:06:17Z (GMT). No. of bitstreams: 1 LEONARDO FALCÃO FEITOSA - DISSERTAÇÃO PPG-CEMat 2014..pdf: 2258061 bytes, checksum: cdc233909fd365937aacd1ef5fa7c2cd (MD5) Previous issue date: 2014-12-29 / Na terapia medicamentosa convencional o fármaco é administrado através de uma forma farmacêutica e produz um nível tecidual do fármaco que não se mantêm dentro da faixa terapêutica por um período prolongado de tempo. Desta forma, o êxito do tratamento vai depender de vários fatores como dosagens precisas e frequentes em horários específicos pré-determinados e adesão do paciente à terapêutica de modo que, a não obediência ao esquema terapêutico, pode resultar em utilização do fármaco em faixa não efetiva ou em níveis tóxicos Devido a grande problemática da manutenção de níveis séricos de fármacos no organismo humano, principalmente quando se tratam se fármacos relacionados ao tratamento de dores de moderadas a intensa, este trabalho propõe o desenvolvimento de membranas porosas a base de quitosana, que é um polímero natural biocompatível, capazes de promover a liberação controlada de fentanil. As matrizes obtidas foram caracterizadas por: MO, MEV, EDS, FTIR, DRX, Ensaio de Intumescimento, Ensaio de Biodegradação e Ensaio de Citotoxicidade. Por MO e MEV verificou-se uma superfície com poros aparentemente interconectados. A partir da análise por EDS pode-se verificar os elementos componentes da quitosana e do fármaco. Por FTIR e DRX notou-se a não alteração dos grupos funcionais e cristalinidade, respectivamente, do material devido a incorporação do fármaco. Baseado nos ensaios de intumescimentos e biodegradação verificou-se a capacidade de controlar as variáveis: razão de intumescimento e taxa de degradação exclusivamente pela variação da concentração de quitosana na membrana porosa. Verificou-se no ensaio de citotoxicidade que as membranas, mesmo com a incorporação do fármaco, não apresentaram citotoxicidade. Baseado nos resultados obtidos pôde-se concluir que é possível sintetizar uma matriz polimérica com promissoras propriedades para carrear fármaco e para testes in vivo. / In conventional medical therapy the drug is administered via a dosage form and produces a tissue level of the drug that is not maintained within the therapeutic range over an extended period of time. Thus, the success of the treatment will depend on several factors such as accurate and frequent dosing at predetermined specific times and patient adherence to therapy so that the non-compliance to the treatment regimen can result in use of the drug in not effective range or toxic levels Due to the great problem of maintaining serum levels of drugs in the human body, especially in the case if drugs related to the treatment of moderate to severe pain, this paper proposes the development of porous membranes chitosan base, which is a biocompatible natural polymer, capable of promoting the controlled release of fentanyl. The matrices obtained were characterized by: OM, SEM, EDS, FTIR, XRD, Swelling test, biodegradation test and Cytotoxicity Assay. For OM and SEM there was apparently a surface with interconnected pores. From the EDS analysis can verify the elements of chitosan and drug. FTIR and XRD noted not to change functional groups of crystallinity and, respectively, of the material due to the incorporation of the drug. Based on swellings and biodegradation tests verified the ability to control the following variables: swelling ratio and degradation rate solely by varying the concentration of the chitosan porous membrane. It was found that the cytotoxicity assay the membranes, even with the incorporation of the drug did not show cytotoxicity. Based on the results obtained it was concluded that it is possible to synthesize a polymer matrix with promising properties to adduce drug and in vivo tests.

Submitted by Emanuel Varela Cardoso (emanuel.varela@ufcg.edu.br) on 2018-06-15T18:55:22Z No. of bitstreams: 1 GILDÊNIA PINTO DOS SANTOS TRIGUEIRO – DISSERTAÇÃO (PPG-CEMat) 2015.pdf: 1530053 bytes, checksum: abc690f9b5acaa9d75775904e546ffe8 (MD5) / Made available in DSpace on 2018-06-15T18:55:23Z (GMT). No. of bitstreams: 1 GILDÊNIA PINTO DOS SANTOS TRIGUEIRO – DISSERTAÇÃO (PPG-CEMat) 2015.pdf: 1530053 bytes, checksum: abc690f9b5acaa9d75775904e546ffe8 (MD5) Previous issue date: 2015-06-19 / O envelhecimento populacional, fenômeno mundial, é um processo iniciado no momento do nascimento e modifica a vida de indivíduos e das estruturas familiares na sociedade. Com o aumento da longevidade há uma tendência ao aparecimento de doenças crônicas, como é o caso do Diabetes Mellitus, um dos principais problemas de saúde pública na atualidade, que abrange elevado número de pessoas acometidas, com mortalidade prematura, além dos custos envolvidos no controle, tratamento e de recuperação das complicações. Este estudo foi realizado com o objetivo de desenvolver membranas de quitosana sem neutralização com incorporação de insulina para liberação controlada deste fármaco. As membranas foram desenvolvidas pelo método de evaporação de solvente e caracterizadas pelas técnicas de Difração de raios-X (DRX), Espectroscopia na Região de Infravermelho com Transformada de Fourier (FTIR), Microscopia Ótica (MO), Microscopia Eletrônica de Varredura (MEV), Tensão Superficial e Intumescimento. A técnica de DRX demonstrou que a não neutralização das membranas atribuiu às mesmas um perfil mais cristalino quando comparado ao perfil da quitosana em pó e que tanto a insulina quanto a reticulação com tripolifosfato de sódio diminuiu o perfil cristalino das mesmas. Com o ensaio de FTIR foi possível perceber um aumento da intensidade dos picos nas regiões entre 1250 e 1600. Através das técnicas de MO e MEV foi possível confirmar a presença da insulina nas membranas encapsulada s pela quitosana. No ensaio de molhabilidade, a presença da insulina e do agente reticulante proporcionou uma diminuição da molhabilidade das membranas quando comparado ao de quitosana sem a insulina e o agente reticulante. Já no de intumescimento ocorreu redução tanto por efeito da adição da insulina quanto da reticulação. Os resultados sugerem que houve a incorporação da insulina na membrana. / Population aging, worldwide phenomenon, is a process that began at birth and changes the lives of individuals and family structures in society. With increasing longevity there is a tendency to the appearance of chronic diseases, such as Diabetes Mellitus, one of the major public health problems today which covers large number of people affected with premature mortality and the costs involved in control treatment of complications and recovery. This study was conducted in order to develop chitosan membranes without neutralization with insulin incorporation for controlled release of the drug. The membranes were developed by the solvent evaporation method and characterized by powder Diffraction X-ray (XRD), spectroscopy in the infrared region Fourier transform (FTIR) spectroscopy, optical microscopy (MO), Scanning Electron Microscopy (SEM), Surface Tension and Swelling. The XRD technique showed that no neutralization of the membrane attributed to a more crystalline same profile when compared to the profile of the chitosan powder, and that both insulin as crosslinking with sodium tripolyphosphate decreased the lens profile of the same. With FTIR test was possible to realize an increase of peak intensity in the regions between 1250 and 1600. Through the OM and SEM techniques it was possible to confirm the presence of insulin encapsulated in the chitosan membranes. In the wetting test, the presence of insulin and crosslinker provided a decrease in wettability compared to the membranes of insulin and chitosan without the crosslinker. Already in the reduction of swelling occurred both as a result of addition of insulin as halftone. The results suggest that insulin was incorporated in the membrane.

Les copolymères à blocs amphiphiles peuvent s’auto-assembler sous forme de vésicules,appelées polymersomes. Ces vésicules ont été développées et étudiées depuis de nombreusesannées notamment pour l’encapsulation et la délivrance contrôlée de médicaments. Depuisquelques temps, elles connaissent des applications dans le domaine du biomimétisme cellulaire.Plus robustes que leurs analogues lipidiques (liposomes), les avantages à utiliser lespolymersomes comme mimes synthétiques de cellules biologiques ne sont plus à démontrer.Ainsi, des structures compartimentées à base de polymères ont été développés comme mimesstructurels de cellules. Ces systèmes ont été utilisés comme bioréacteurs, avec la réalisation deréactions chimiques ou enzymatiques en cascade en milieu confiné. Toutefois, l’un desobstacles qu’il reste à franchir est de trouver des moyens simples et efficaces pour déclencherla réaction au sein de ces systèmes. C’est dans ce contexte que s’inscrivent les travaux de cettethèse. Une membrane synthétique asymétrique à base de lipide et polymère a été développée etla méthode d’émulsion-centrifugation a été utilisée pour produire des systèmes compartimentésbiomimétiques. De plus, deux approches différentes ont été suivies pour provoquer la libérationcontrôlée d’espèces encapsulées, l’une utilisant la température et l’autre la lumière. Enfin, desétudes de co-encapsulation de cellules synthétiques (polymersomes) et biologiques au sein demilieux 3D ont été réalisées dans le but d’évaluer leur compatibilité et la possibilité de les cocultiver. / Amphiphilic block copolymers can self-assemble into vesicles, also called polymersomes.These vesicles have been developed and studied for many years especially in the field of drugloading and controlled release. More recently, their use as cell mimics have attracted a lot ofattention, mainly because polymersomes exhibit many advantages in contrast to their lipidicanalogues (liposomes). In such, compartmentalized polymer systems have especially beendeveloped as structural mimics of cells. These systems have found applications as bioreactorsthat can confine cascade chemical or enzymatic reactions. However, a major goal that stillremains to achieve is to find ways to trigger the beginning of these chemical reactions insidethe compartmentalized structures. The work carried out during this PhD thesis was actually totackle this challenge. A synthetic asymmetric lipid – polymer membrane, that mimics themembrane of biological cells was developed and the emulsion-centrifugation protocol wasfollowed to prepare biomimetic compartmentalized structures. In addition, two different waysto control the independent release of multiple species from individual compartments weredeveloped, based on temperature or light activation. Lastly, co-encapsulation of synthetic cells(polymersomes) and biological cells were performed in 3D media with the aim to study theircompatibility for co-culture experiments.

Submitted by Jos? Henrique Henrique (jose.neves@ufvjm.edu.br) on 2017-09-12T20:11:13Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) regina_inez_souza.pdf: 2322505 bytes, checksum: fb22e286692f3f78b323a1aa5767c86b (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2017-09-18T13:03:41Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) regina_inez_souza.pdf: 2322505 bytes, checksum: fb22e286692f3f78b323a1aa5767c86b (MD5) / Made available in DSpace on 2017-09-18T13:03:41Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) regina_inez_souza.pdf: 2322505 bytes, checksum: fb22e286692f3f78b323a1aa5767c86b (MD5) Previous issue date: 2017 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / Na ind?stria farmac?utica, os pol?meros s?o bastante utilizados em sistemas para libera??o controlada de f?rmacos, por serem capazes de liber?-los efetivamente no local alvo, aumentando os benef?cios terap?uticos e minimizando os efeitos colaterais. Entre os pol?meros utilizados para essa finalidade, tem-se o poli(3-hidroxibutirato) (PHB) pertencente a classe dos poli(hidroxialcanoatos), sendo um pol?mero de origem microbiana, que destacase por ser biorreabsorv?vel e biocompat?vel. Quando utilizado em misturas f?sicas com outros pol?meros, as denominadas blendas, modifica-se propriedades f?sicas, mec?nicas e biol?gicas do PHB para aumentar sua aplicabilidade. Nesse sentido, o propilenoglicol (PPG) foi utilizado para prepara??o de blendas PHBPPG (90/10). O objetivo do trabalho foi preparar e estudar filmes polim?ricos constitu?dos por PHB e PHBPPG (90/10) contendo 1% e 5% de Snitrosoglutationa (GSNO), um doador de ?xido n?trico (NO) bem como sintetizar o f?rmaco e avaliar sua estabilidade ap?s armazenamento a 23?C, 4?C e -18?C durante 90 dias por an?lise t?rmica e por espectroscopia na regi?o do infravermelho. Os filmes obtidos contendo GSNO foram caracterizados por an?lise t?rmica, espectroscopia no infravermelho e avaliou-se o perfil de libera??o in vitro dos mesmos. A citotoxicidade dos extratos das matrizes constitu?das somente por PHB e PHBPPG (90/10) foi avaliada sobre c?lulas mononucleares do sangue perif?rico (PBMC) e leuc?citos totais pelo m?todo de exclus?o com azul de Tripan e sobre hem?cias pela avalia??o da atividade hemol?tica. Os resultados da an?lise t?rmica e infravermelho mostraram que a melhor forma de armazenamento de GSNO ? em 4?C e -18?C. As matrizes polim?ricas de PHB e da blenda PHBPPG (90/10) contendo 1% e 5% de GSNO, avaliadas por an?lise t?rmica foram capazes de liberar NO e apresentaram-se mais est?veis termicamente quando comparados aos filmes de PHB e da blenda sem o f?rmaco. O perfil de libera??o dos filmes de PHB e da blenda PHBPPG (90/10) mostrou que h? uma libera??o r?pida inicial de GSNO nas 24 horas iniciais seguido por um padr?o de libera??o controlada no per?odo de 1 a 8 dias para os filmes contendo 5% de GSNO, sendo o filme da blenda PHBPPG (90/10) contendo 5% de f?rmaco, o que apresentou maior porcentagem de libera??o no per?odo avaliado. Extratos provenientes dos filmes de PHB e da blenda PHBPPG (90/10) n?o apresentaram car?ter citot?xico por n?o induzirem hem?lise das hem?cias e n?o reduzirem a viabilidade celular de PBMCs e leuc?citos totais. As blendas desenvolvidas neste trabalho possuem a capacidade de libera??o controlada e in situ de ?xido n?trico, e possuem aplica??o potencial, por exemplo, no revestimento de stents coronarianos para preven??o da restenose p?s-angioplastia. / Disserta??o (Mestrado) ? Programa de P?s-gradua??o em Ci?ncias Farmac?uticas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2017. / Polymers are widely used for controlled drug release systems improving the therapeutic benefits and minimizing side effects by the pharmaceutical industry due their capability of releasing it effectively at the target site. Among the polymers used for this purpose there is poly(3-hydroxybutyrate, PHB), a polymer from microbial origin of the poly(hydroxyalkanoate) class that is both bioresorbable and biocompatible. When used as a physical blends with other polymers several properties of PHB (physical, mechanical and biological) could be modified to increase their applicability. To produce blends with PHB the propyleneglycol (PPG) was used to prepare PHBPPG blends (90/10). The aim of this work was to prepare and study polymeric films composed by PHB and PHBPPG (90/10) containing 1% and 5% S-nitrosoglutathione (GSNO), a nitric oxide (NO) donor. The GSNO was synthesized and had its stability evaluated after storage at 23 ? C, 4 ? C and -18 ? C for 90 days by thermal analysis and infrared spectroscopy. The polymer materials containing GSNO were characterized by thermal analysis, infrared spectroscopy and also their drug release capability was evaluated. The cytotoxicity of matrices constituted by PHB and PHBPPG (90/10) was evaluated on peripheral blood mononuclear cells (PBMC) and total leukocytes by the exclusion method with Tripan blue and on red blood cells by the evaluation of hemolytic activity. The thermal and infrared analysis showed that the best form of GSNO storage is at 4 ? C and -18 ? C. Polymeric matrices of PHB and PHBPPG (90/10) containing 1% and 5% of GSNO, were able to release NO and were more thermally stable when compared to PHB and blends without the drug. The release profile of the PHB and PHBPPG blends (90/10) showed an initial fast release of GSNO at the initial 24 hours followed by a controlled release pattern in the period of 1 to 8 days for materials containing 5% of GSNO. The PHBPPG (90/10) blends containing 5% of drug presented the highest percentage of release in the evaluated period. The PHB and PHBPPG (90/10) blends did not present cytotoxic effects. The studied materials did not induced hemolysis of the red blood cells and did not reduced the cellular viability of PBMCs and total leukocytes. The developed blends are capable to exert the in situ controlled-release of nitric oxide and can potentially be used for example to coat coronary stents and thus help to prevent post-angioplasty restenosis.

Ce travail a pour vocation d’évaluer la potentialité de différents hydrogels sensibles au glucose pour la délivrance d’insuline en vue de développer de nouveaux traitements du diabète. Les systèmes doivent être biocompatibles et pouvoir se résorber in vivo. Pour cela, nous avons choisi d’utiliser un polysaccharide, l’acide hyaluronique (HA), dégradable par voie enzymatique. La réticulation est obtenue par une polymérisation radicalaire de méthacrylates, ou par couplage thiol-ène. La sensibilité au glucose est apportée par l’introduction de fonctions acide phénylboronique (PBA), connues pour former des liaisons ester réversibles avec les diols des saccharides. Deux types de gels sont étudiés : les gels simples où le PBA seul est greffé sur le HA, et des gels doublement réticulés où des motifs maltose sont greffés sur le HA et forment un deuxième réseau, dissociable par ajout de glucose.Dans ce travail, nous avons cherché à démontrer les capacités de cette classe de matériaux à encapsuler et délivrer l’insuline selon les pharmacocinétiques adaptées à l’application. La cinétique étant dépendante de la taille des gels, nous avons travaillé à plusieurs échelles, du macroscopique à l’échelle nanométrique, principalement visée pour une libération dans la circulation sanguine. Des particules de gel sont préparées à des échelles nanométriques et micrométriques grâce à des émulsions eau-dans-huile, obtenues respectivement par homogénéisation à haute pression et par microfluidique. Les gouttes formées servent de micro/nanoréacteurs où se produit la réticulation photoamorcée du HA préalablement modifié. L’échelle micrométrique a été choisie pour étudier plus précisément les interactions de l’insuline ainsi que des protéines modèles avec les matrices, grâce à la microscopie confocale qui permet de sonder la distribution des protéines dans le réseau. Nous avons ainsi étudié les propriétés d’encapsulation et de libération ainsi que les propriétés de gonflement des gels. L’impact de la composition et de la structure des gels est ainsi mis en évidence permettant d’optimiser les choix de formulation pour proposer une solution de libération contrôlée de l’insuline. Enfin l’encapsulation et le relargage d’insuline en présence de sucre est étudiée de manière quantitative pour des macrogels, dont la composition a été optimisée. / This work aims to evaluate potential glucose sensitive hydrogels formulations as new medicine to treat diabetes. The gels have to be biocompatible and bioresorbable in vivo. To do so, we choose matrices of polysaccharide enzymatically degradable made of hyaluronic acid (HA). Crosslinking of the HA is done by radical polymerization reactions using methacrylates or thiol-ene chemistry. Glucose sensitivity is introduced thanks to phenylboronic acid moieties (PBA). PBAs are known for their ability to create reversible bonding with diols from saccharides. Two kind of gels are studied: simples ones where PBAs are grafted on the matrix, and doubly crosslinked ones where maltose groups grafted on HA form a second network, which can dissociate upon glucose addition. We investigated the ability of these materials to encapsulate and deliver insulin with the good pharmacokinetics. As kinetics depend on gel sizes, we worked at different scales, from macroscopic to nanometric scale, which allows release in the blood stream. Nano and microgels are prepared thanks to water-in-oil emulsions using respectively high pressure homogeneiser or microfluidic devices. Droplets formed are used as nano/microreactors where crosslinking of modified HA is photoinitiated. Micrometric scale is chosen to study interactions between insulin and model proteins with gel matrices, using confocal microscopy. This technique allows to study composition and structural effects. Encapsulation and release of proteins are studied as well as swelling variations. Then, encapsulation and release of insulin upon addition of monosaccharide is investigated quantitatively for macrogels, after formulation optimization.

Orientador: Prof. Dr. Wendel Andrade Alves / Tese (doutorado) - Universidade Federal do ABC, Programa de Pós-Graduação em Nanociências e Materiais Avançados, 2015. / Os biopolímeros mostram-se materiais promissores na construção de dispositivos para aplicações na área biomédica. Dentro desta classe a policaprolactona vêm sendo amplamente empregada em sistemas de liberação controlada, uma vez que permite a incorporação de drogas preservando a atividade farmacológica. Neste trabalho, apresentamos a proposta de um material híbrido composto por policaprolactona (PCL) e micro-/nanotubos de L,L-difenilalanina (MNTs-FF). O biomaterial foi avaliado à temperatura ambiente nas concentrações de 0% a 50% de MNTs-FF. As propriedades morfológicas e estruturais dos compósitos foram investigadas por diferentes técnicas analíticas, espectroscópicas e microscópicas. Os resultados obtidos mostraram que, o peptídeo promoveu variações microestruturais na rede polimérica, impactando no diâmetro médio das fibras (~570-360 nm), na cristalinidade (34,6 - 6,6%) e na porosidade (74 - 50%). Como consequência, tais variações foram associadas ao comportamento elástico-plástico da matriz. O aumento da concentração de MNTs-FF contribuiu para um maior módulo de Young para as fibras de PCL (12,47-18,96 MPa). Testes de biodegradação enzimática mostraram uma perda significativa de massa para as membranas com peptídeos em relação ao polímero puro. Os compósitos de MNTs-FF/PCL foram avaliados na liberação controlada do fármaco lipofílico, benzocaína. As membranas apresentaram uma eficácia progressiva de liberação de ~13 horas, sendo este um resultado superior ao gel disponível no mercado atualmente. Logo, o compósito exibiu elevada resistência mecânica e características biodegradáveis, sendo propriedades favoráveis na aplicação como sistemas carreadores de fármacos. / The biopolymers appear to be promising materials for the development of devices for the biomedicine area. Within this class, the polycaprolactone has been widely used in systems of controlled liberation, once it allows the incorporation of drugs preserving the pharmacological activity. In this essay, we propose a hybrid material composed by polycaprolactone (PCL) and micro-/nanotubes of L,L-diphenylalanine (FF-MNSs). The biomaterial was evaluated under room temperature in the concentrations from 0% to 50% of FF-MNSs. The morphological and structural properties were investigated by different analytical, spectroscopical and microscopical techniques. The results showed that the peptide promoted microstructural variations in the polymeric net, having impact on the average diameter of the fibers (~570-360 nm), in the crystallinity (34.6- 6.6%) and in the porosity (74 - 50%). As a result, such variations were associated to the elastic-plastic behavior of the matrix. The increase in concentration of FF-MNSs contributed for a bigger Young module for the PCL fibers (12.47-18.96 MPa). Enzymes biodegrading tests showed a significant loss of mass for the membranes with peptides comparing to the pure polymer. The composite of FF-MNSs/PCL were evaluated in the controlled liberation of the lipophilic drug, benzocaine. The membrane presented a progressive liberation efficiency of ~13 hours, being this a superior result to the gel available in the market currently. Therefore, the composite showed high mechanical resistance and biodegradable features, which are favorable features in its use as drug carrier systems.

Submitted by ANA KARLA PEREIRA RODRIGUES (anakarla_@hotmail.com) on 2017-08-02T15:41:08Z No. of bitstreams: 1 arquivototal.pdf: 5765942 bytes, checksum: 274481954c5d791369e586a0fa87060c (MD5) / Made available in DSpace on 2017-08-02T15:41:08Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 5765942 bytes, checksum: 274481954c5d791369e586a0fa87060c (MD5) Previous issue date: 2016-02-25 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Polymer blends are a prompt and economical way to obtain new materials and have attracted considerable interest. Xanthan gum (GX) and poly (vinyl alcohol) (PVA) are polymers of great interest because of their properties. The high hydrophilic nature of these materials limits their applications, so they need to be submitted to the crosslinking process. In this work were prepared and characterized polymeric films (1% w / v) consisting of xanthan gum and poly (vinyl alcohol) without crosslinking agent and crosslinked with citric acid (CA) by casting for use in controlled drug release. The infrared analysis demonstrated possible interactions between the polymers in the blend and the incorporation of crosslinker into the polymer matrix. The scanning electron microscope revealed that the surfaces of the films are smooth and homogeneous even with the addition of crosslinking agent. The solubility, swelling and permeability to water vapor tests showed synergism between properties of polymers in the blend and citric acid attributed to the film water resistance. The compositions are stable in an inert atmosphere (N2), and films crosslinked with citric acid exhibited better thermal stability when compared with no crosslinking. The thermal degradation kinetics study complemented the results of thermal analysis showing that the PVA films are more stable and the crosslinking agent has improved thermal properties of the films. Biodegradability tests in soil revealed greater degradation to the polymer blends over a period of 160 days. The films exhibited no antimicrobial activity against the microorganisms studied. The application of crosslinked films with citric acid on controlled drug release showed that acetaminophen, propranolol and fluconazole release mechanism was controlled primarily by diffusion, swelling and relaxation of the polymer chains, with constant release profiles for 24 h, demonstrating that the developed films are promising materials for controlled drug release. / Blendas poliméricas representam uma forma rápida e econômica para obtenção de novos materiais e vêm atraindo bastante atenção. A goma xantana (GX) e o poli (álcool vinílico) (PVA) são polímeros de interesse devido as suas propriedades. O alto caráter hidrofílico desses materiais limitam suas aplicações, por isso eles precisam passar pelo processo de reticulação. Neste trabalho foram preparados e caracterizados filmes poliméricos (1% m/v) constituídos por goma xantana e poli (álcool vinílico) sem agente reticulante e reticulados com ácido cítrico (AC) pelo método da evaporação do solvente para aplicação na área de liberação controlada de fármacos. Os dados de espectroscopia de infravermelho sugeriram possíveis interações entre os polímeros na blenda e a incorporação do reticulante na matriz polimérica. A microscopia eletrônica de varredura revelou que as superfícies dos filmes são lisas e homogêneas, mesmo com a adição do agente reticulante. Os ensaios de solubilidade, intumescimento e permeabilidade ao vapor de água mostraram o sinergismo das propriedades dos polímeros na blenda e que o ácido cítrico atribuiu aos filmes resistência à água. As composições mostraram-se estáveis em atmosfera inerte (N2), e os filmes reticulados com ácido cítrico exibiram melhor estabilidade térmica quando comparados com os sem reticulante. O estudo de cinética de degradação térmica complementou os resultados de análise térmica mostrando que os filmes de poli (álcool vinílico) são mais estáveis e que o agente reticulante aumentou as propriedades térmicas dos filmes. Os ensaios de biodegradabilidade em solo mostraram maior degradação para as blendas poliméricas em um período de 160 dias. Os filmes não demonstraram atividade antimicrobiana frente aos microrganismos estudados. A aplicação dos filmes reticulados com ácido cítrico na área de liberação controlada mostrou que o mecanismo de liberação de paracetamol, propranolol e fluconazol foi controlado principalmente por difusão, intumescimento e relaxamento das cadeias poliméricas, apresentando perfis de liberação constantes em 24 h, demonstrando que os filmes desenvolvidos são materiais promissores para liberação controlada de fármacos.

Made available in DSpace on 2014-12-17T15:01:17Z (GMT). No. of bitstreams: 1 BentoPCN.pdf: 1568863 bytes, checksum: bd484a66a36dd1be9ccc75015b40e5e8 (MD5) Previous issue date: 2009-03-05 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Currently, studies in the area of polymeric microcapsules and nanocapsules and controlled release are considerably advanced. This work aims the study and development of microcapsules and nanocapsules from Chitosan/MDI, using a new technique of interfacial polycondensation combined to spontaneous emulsification, for encapsulation of BZ-3. It was firstly elaborated an experimental design of 23 of the particle in white without the presence of BZ-3 and Miglyol, where the variables were the concentrations of MDI, chitosan and solvent. Starting from the data supplied by the experimental design was chosen the experiment with smaller particle diameter and only added like this BZ-3 and Miglyol. The suspension containing concentrations of 6.25 mg/mL, 12.5 mg/mL, 18.75 mg/mL, 25 mg/mL of BZ-3 were prepared, nevertheless, during the storage time, these formulations presented drug precipitates in the suspensions of 18.75 mg/mL and 25 mg/mL of BZ-3. This apparition of precipitate was attributed to the diffusion of BZ-3 for the aqueous phase without any encapsulation, suggesting so the use of the smaller concentrations of the BZ-3. The suspension containing 6.25mg/mL of BZ3 presented average size of 1.47μm, zeta potential of 61 mV, pH 5.64 and this sample showed an amount of BZ-3 and drug entrapment of 100 %. The suspension containing 12.5mg/mL of BZ-3 presented average size of 1.76μm, zeta potential of 47.4 mV, pH 5.71 and this sample showed an amount of BZ-3 and drug entrapment of 100 %. Then, showing such important characteristics, these two formulations were chosen for futher continuity to the study. These formulations were also characterized by the morphology, FTIR, stability for Turbiscan, DSC and a study of controlled release of the BZ-3 was elaborated in different receiving means / O presente trabalho visou o estudo e desenvolvimento de um sistema micro e nanoestruturado de quitosana reticulada por diisocianato, pela t?cnica de policondensa??o interfacial combinada com emulsifica??o espont?nea, para encapsula??o de benzofenona-3 (BZ-3), um filtro solar qu?mico. Foi elaborado primeiramente um planejamento experimental de 23 para desenvolvimento da formula??o de part?culas de quitosana e MDI (4,4 -difenil metano diisocianato), onde as vari?veis foram ?s concentra??es de MDI, de quitosana e do solvente. A partir dos dados fornecidos pelo planejamento experimental, optou-se pelas condi??es de processo e formula??o capazes de gerar o menor di?metro de part?cula. O estudo prosseguiu com a incorpora??o de BZ-3 e Miglyol (n?cleo das c?psulas formadas). Suspens?es de nanoc?psulas com concentra??es de 6,25 mg/mL, 12,5 mg/mL, 18,75 mg/mL e 25 mg/mL de BZ-3 foram preparadas, por?m durante o per?odo de armazenamento ocorreu o aparecimento de precipitados cristalinos, nas suspens?es de 18,75 mg/mL e 25 mg/mL de BZ-3. Este aparecimento de precipitados cristalinos foi atribu?do ? difus?o da BZ-3 para a fase aquosa n?o ocorrendo sua encapsula??o. A suspens?o contendo 6,25 mg/mL de BZ-3 apresentou di?metro m?dio de 1,47μm, potencial zeta de 61 mV, pH de 5,64 e teor de encapsula??o pr?ximos a 100 %. A suspens?o contendo 12,5mg/mL de BZ-3 apresentou di?metro m?dio de 1,76μm, potencial zeta de 47,4mV, pH 5,71 e teor de encapsula??o pr?ximos a 100 % e foi selecionada juntamente com a de 6,25 mg/mL para a continuidade do estudo. Estas formula??es foram caracterizadas tamb?m pela morfologia, turbidimetria, espectroscopia de absor??o na regi?o do infravermelho, DSC e foi elaborado um estudo de libera??o controlada do f?rmaco em diferentes meios receptores. Em conclus?o, o conjunto dos resultados obtidos demonstra que estas formula??es s?o sistemas promissores para a aplica??o cut?nea de filtros solares