Este estudo tem como objetivo central avaliar a influência da secagem por aspersão de nanocápsulas de núcleo lipídico contendo tretinoína nos perfis in vitro de liberação e de penetração cutânea deste fármaco a partir de hidrogéis. Esses experimentos foram conduzidos empregando-se células de difusão de Franz, pele de abdome de porcos (fêmeas), regime de aplicação de doses infinitas e meio receptor composto por tampão fosfato pH 7,4 e etanol (70:30). A secagem por aspersão das suspensões de nanocápsulas, utilizando PVP e lactose (1:1, m/m) a 10% como adjuvantes, forneceu produtos com bons perfis de dispersão em água, bons rendimentos (próximos a 70%), baixos teores de substâncias voláteis, e teores do fármaco acima de 92%. O tipo de produto intermediário, suspensão aquosa ou respectivo pó, utilizado na produção de hidrogéis (G-LNC-TTN e G-LNC-TTN-SD, respectivamente) não influenciou no perfil de liberação in vitro da tretinoína, que se ajustou ao modelo de Higuchi. No estrato córneo houve diferenças nas quantidades de tretinoína penetradas a partir das duas formulações. O G-LNC-TTN levou a uma retenção exponencial do fármaco nessa camada, enquanto para o G-LNC-TTN-SD isso não ocorreu. Essa diferença foi associada à forma de organização das nanocápsulas na matriz do gel. Na epiderme e na derme, ambas as formulações permitiram a chegada de pequenas e constantes quantidades de tretinoína. No compartimento receptor da célula de Franz o fármaco não foi detectado. A pequena permeação da tretinoína para as camadas mais profundas da pele e para o meio receptor são indicativos de baixa absorção sistêmica, e também podem contribuir para a diminuição dos efeitos adversos associados à terapia tópica com essa substância. A secagem das suspensões de nanocápsulas de núcleo lipídico, nas condições utilizadas, forneceu um intermediário em potencial para a produção de formas farmacêuticas semissólidas contendo tretinoína. / This study’s central goal is to assess the influence of spray-drying lipid core nanocapsules on tretinoin in vitro release profiles as well as skin penetration/permeation from hydrogels. These experiments were conducted employing Franz diffusion cells, pig abdominal skin (female), infinite doses regimen and receptor medium composed of phosphate buffer pH 7.4 and ethanol (70:30). Spray-drying of the nanocapsules suspensions, using PVP and lactose (1:1, m/m) at 10% (m/v) as drying adjuvant provided powders with good water dispersion profiles, good yields (around 70%), low volatile substances contents, in addition to drug contents above 92%. Interchanging intermediate products, aqueous suspension or respective powder, used in hydrogel formulation (G-LNC-TTN and G-LNC-TTN-SD, respectively) caused no influence on tretinoin in vitro release profile which was adjusted by Higuchi model. In corneum stratum there were differences in tretinoin quantities which penetrated from those formulations. The G-LNC-TTN provided an exponential retention of the drug on this skin’s layer, although G-LNC-TTN-SD did not. This difference was associated with the nanocapsules organization form in hydrogel matrix. In epidermis and dermis both formulations allowed permeation of constant and low tretinoin quantities. Moreover, at receptor fluid the drug was not detected. The low tretinoin permeation for deeper skin layers and for receptor fluid is low systemic absorption indicative, furthermore, may contribute in reducing adverse effects associated with tretinoin topical therapy. In given conditions, spray-drying of lipid core nanocapsules provided a potential intermediate for production of semi solids pharmaceutical forms containing tretinoin.

The high demand for an increase in performance and at the same time loweringthe emissions is forcing the automotive industry to increase the efficiency of thevehicles. This demand lead to a problem called knock, which often is the limitingfactor when increasing the efficiency of the engine. Knock occurs when theunburned gases inside the combustion chamber self-ignites due to the increasingpressure and temperature.This thesis investigates if it is possible to predict knock with a physicallybased knock model. The model consist of several sub-models such as pressuremodel, temperature model and knock model. The models are built by using measureddata and the goal is to get an independent knock prediction model that canfind the limited ignition angle that will cause knock.The results shows that an analytic pressure model can simulate a measuredpressure curve. But when it comes to predicting knock, there is an uncertaintywhich can be improved by changing the modelling strategy and making the modelsmore accurate.

Disponibiliza??o em conte?do parcial do trabalho, conforme Termo de Autoriza??o. / Submitted by Jos? Henrique Henrique (jose.neves@ufvjm.edu.br) on 2017-02-14T19:00:46Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) lays_fernanda_nunes_dourado_parcial.pdf: 389665 bytes, checksum: 2289d8ac4ca389d5cdaf516878ddae78 (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2017-03-06T12:24:50Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) lays_fernanda_nunes_dourado_parcial.pdf: 389665 bytes, checksum: 2289d8ac4ca389d5cdaf516878ddae78 (MD5) / Made available in DSpace on 2017-03-06T12:24:50Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) lays_fernanda_nunes_dourado_parcial.pdf: 389665 bytes, checksum: 2289d8ac4ca389d5cdaf516878ddae78 (MD5) Previous issue date: 2016 / Na ind?stria farmac?utica, os pol?meros s?o capazes de desempenhar a fun??o de matriz para libera??o controlada de f?rmacos. Isto tem como vantagem a minimiza??o dos efeitos adversos dos medicamentos e a otimiza??o do tratamento. Entre os pol?meros utilizados para tal finalidade, tem-se o poli(3-hidroxibutirato) (PHB) conhecido por sua origem natural, um material que se degrada a produtos n?o t?xicos para o organismo, o que garante o seu emprego como biomaterial. Quando utilizado em associa??o a outros pol?meros, s?o denominados Blendas, essas misturas modificam as caracter?sticas f?sico-qu?micas dos pol?meros para serem empregados em finalidades diversas. Desta forma este trabalho teve como objetivo o desenvolvimento de uma matriz polim?rica capaz de ser utilizada para libera??o controlada de f?rmacos. Para tal, foram produzidas duas membranas diferentes uma de PHB e outra de Blenda Poli (3-hidroxibutirato)/Polipropilenoglicol, PHB/PPG (90:10), com concentra??es diferentes de f?rmaco, contendo 5% e 25% em massa. O f?rmaco modelo foi a Sinvastatina. Estes dispositivos foram produzidos por dissolu??o seguida de evapora??o do solvente, formando filmes de 0,5 mm de di?metro que foram analisados quanto a sua degrada??o in vitro e in vivo, em implantes subcut?neos. Os materiais foram analisados utilizando espectroscopia na regi?o do infravermelho, termogravimetria, microscopia eletr?nica de varredura e por testes histol?gicos. Os filmes ? base de PHB, apresentaram degrada??o in vitro e in vivo mais lenta quando comparados ?s blendas, no entanto em ambos os casos, os materiais que continham maior percentual de Sinvastatina apresentaram maior degrada??o e libera??o do f?rmaco. As l?minas histol?gicas revelam a presen?a do tecido em torno dos dispositivos e aus?ncia de inflama??o o que comprova a biocompatibilidade dos materiais estudados. / Disserta??o (Mestrado) ? Programa de P?s-gradua??o em Ci?ncias Farmac?uticas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2016. / In the pharmaceutical industry, the polymers are able to drive the controlled release of drugs. Its brings the advantage of minimizing adverse effects of medicines and optimization of treatment. Among the polymers used for this purpose the poly (3-hydroxybutyrate) has known for their natural origin, its degradation to non-toxic effects to the life tissue which ensures their use as subcutaneous implants. A blend is a mixture of different polymers, these mixtures are able to modify the physicochemical characteristics of the polymers for several uses. This study aimed to develop a polymer matrix can be used as a way for controlled release of drugs. For this purpose, two different membranes were produced, the PHB and a Poly(3-hydroxybutyrate)/Polypropylene glycol blends, PHB/PPG (90:10), with different concentrations of drug with 5% and another 25%. The simvastatin was chosen as a model. These devices were manufactured by casting to form films of 0.5 mm diameter that were analyzed for in vitro and in vivo degradation tests using subcutaneous implants. The materials were analyzed using infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy and histological tests. The films based on PHB presented a slower degradation in vitro and in vivo degradation tests when compared to the blends, however in both cases those materials containing a higher percentage of simvastatin has shown the higher degradation and release of the drug. The histological sections showed a tissue colonization and absence of inflammation which demonstrates the biocompatibility of the implants.

J’avais dix ans. C’était après la guerre et l’Iran était sous embargo. A l’école je n’avais que deux crayons pour écrire mes devoirs, un noir et un rouge. Les deux étaient ornés du symbole d’une marque, un crocodile noir. Cela était aussi un gage de qualité. Mes crayons crocodiles écrivaient bien. J’étais habituée à les voir, mes crocodiles. Puis je passais beaucoup de temps avec ma tante. Elle faisait de la couture. Je jouais avec les restes des tissus. J’étais fascinée par les couleurs et par des formes que je créais avec ces bouts de tissu. J’ai sans doute commencé mes premiers collages à ce moment-là. Plus tard quand je suis devenue peintre, les animaux et les couleurs étaient la base de mes peintures. Parmi ces animaux le crocodile surgissait sans que je sois consciente de la raison de cette apparition. Un jour en réfléchissant je me suis souvenue de mes crayons d’enfance ! Quand j’ai commencé à peindre, les limites et les contraintes en Iran ne me permettaient pas de m’exprimer librement. Alors le jeu d’enfance que j’avais repris dans le style de ma peinture, me rendait celle-ci agréable et ludique. J’avais mes couleurs et le jeu, et j’exprimais ce que je voulais ; j’avais réussi à trouver un langage d’expression ludique et fort et j’en étais ravie. Je n’étais pas la seule à prendre le jeu comme moyen de contourner les limites et la censure. Déjouer les limites par le jeu était le centre de notre travail. La réflexion sur l’irruption du jeu dans l’art visuel contemporain et en particulier en Iran est devenu le sujet central de ma réflexion et de mon interrogation sur les raisons qui nous ont conduit à nous exprimer ainsi. Je l’ai donc choisie comme le sujet de ma thèse. [...] / I was ten years old. It was after the war and Iran was embargoed. At school I only had two pencils to write my homework, one black and one red. Both were decorated with the symbol of a brand, a black crocodile. It was also a guarantee of quality. My crocodile pencils wrote well. I was used to seeing them, my crocodiles. Then I spent a lot of time with my aunt. She was sewing. I played with the remains of the fabrics. I was fascinated by the colors and shapes that I created with these pieces of fabric. I probably started my first collages at that time. Later when I became a painter, animals and colors were the basis of my paintings. Among these animals the crocodile arose without my being aware of the reason for this apparition. One day while thinking I remembered my childhood pencils! When I started painting, the limits and constraints in Iran did not allow me to express myself freely. Then the childhood game that I had taken in the style of my painter, made me this one pleasant and playful. I had my colors and the game, and I expressed what I wanted; I had managed to find a language of playful and strong expression and I was delighted. I was not the only one to take the game as a way to get around the limits and the censure. Breaking the boundaries through play was the center of our work. The reflection on the irruption of the game in the contemporary visual art and in particular in Iran became the central subject of my reflection and my interrogation on the reasons which led us to express ourselves thus. I chose it as the subject of my thesis. [...]

Micropartículas formadas por blendas de P(HB-HV) com PCL apresentam aumento da porosidade com o aumento do percentual de PCL. Considerando-se a influência de poros na velocidade de liberação de fármacos, bem como a ausência de estudos que correlacionem quantitativamente perfis de liberação e características morfológicas de micropartículas de P(HB-HV), o objetivo desse trabalho consistiu na preparação e caracterização de micropartículas de P(HB-HV) e P(HB-HV)/PCL em diferentes proporções, buscando-se essa correlação para perfis de liberação de dois fármacos-modelo lipofílicos e ionizáveis (diclofenaco e indometacina). A técnica de emulsificação/evaporação do solvente foi empregada na preparação das micropartículas, com eficiência de encapsulação de cerca de 85 %. As micropartículas apresentaram formato esférico e interior oco. O diâmetro médio dos sistemas (122 μm a 273 μm) foi dependente da concentração de PCL, apresentando polidispersão inferior a 1,8. A metodologia de preparação das micropartículas influenciou no processo de cristalização do P(HB-HV). Adicionalmente, a indometacina atuou como um antiplastificante desse polímero. A liberação dos fármacos foi sustentada, cuja velocidade aumentou com o aumento da concentração de PCL. Tais perfis foram descritos por uma equação biexponencial. A partir do ajuste dos dados de liberação à equação de Baker-Lonsdale, determinou-se o produto DCs,m entre o coeficiente de difusão aparente dos fármacos e sua solubilidade na matriz. O logaritmo natural de DCs,m foi diretamente proporcional ao percentual de PCL. Além disso, o fator de porosidade-tortuosidade relativo mostrouse inversamente proporcional à razão entre a área superficial e o quadrado do raio das micropartículas. A partir dos resultados desse estudo, sugeriu-se que o diclofenaco encontra-se associado às micropartículas de P(HB-HV) e P(HB-HV)/PCL na forma de aglomerados nanométricos, enquanto que a indometacina é solubilizada pela matriz polimérica. Além disso, demonstrou-se que o controle da liberação pode ser efetuado pela modulação da morfologia das micropartículas. / Microparticles composed of P(HB-HV)/PCL demonstrate an increase in porosity with a concomitant increase in PCL concentration. Several reports indicate that pores are able to increase the rate of drug delivery. Up to now, there is a lack of information regarding the correlation between the drug release profiles and the P(HB-HV) microparticles morphology. In this context, the objectives of the current work were the preparation and the characterization of microparticles composed of P(HB-HV) and P(HB-HV)/PCL in different proportions in order to obtain a correlation between the microparticles morphology and the release profiles, using two lipophilic and ionizable drug-models, diclofenac and indomethacin. Microparticles, prepared by emulsion/solvent evaporation technique, presented encapsulation efficiencies about 85 %. The SEM analyses showed hollow and spherical microparticles. Their average diameters (122 μm to 273 μm) were dependent on the PCL concentration, and the polydispersity values were lower than 1.8. DSC analyses showed that the preparation process influenced on the P(HB-HV) crystallization. Additionally, Tg values indicated that indomethacin was an antiplasticizer agent of P(HB-HV). The drug release from the microparticles showed sustained profiles. The release rate was faster with the increase in the PCL concentration. The profiles were described by a biexponential equation. After the adjustment of the release data to the Baker- Lonsdale equation, it was possible to determine the value of the product between the drug apparent diffusion coefficient and the drug solubility in the matrix (DCs,m) for each formulation. The logarithms of such values were directly proportional to the PCL percentual. Besides, the relative porosity-tortuosity factor of the microparticles was inversely proportional to the ratio of their specific surface areas and the square of their radius. Based on the obtained results, it was proposed that the diclofenac is associated to the microparticles as nanometric agglomerates, while indomethacin was molecularly dispersed in the polymeric matrix. In addition, results demonstrated that the release can be modulated by controlling the microparticle morphology.

Made available in DSpace on 2015-03-26T13:30:26Z (GMT). No. of bitstreams: 1 texto completo.pdf: 537077 bytes, checksum: 87b9c3bc305f8241b417b885c367acb1 (MD5) Previous issue date: 2009-07-24 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / Several papers have been published recently to investigate the relationship between ecosystem functioning and biodiversity, even though a conclusive position regarding this subject is still lacking. This study tests the relationship between litter decomposition and nutrient release rates with litter arthropod species richness and composition. The hypotheses that (i) sites with higher litter arthropod species richness have higher decomposition and nutrient release rates, and (ii) litter arthropod species composition affects decomposition and nutrient release rates were tested, in a secondary re-growth forest in Brazil. Litter decomposition rates did not respond to litter arthropod species richness, suggesting a redundancy between arthropod species. This may signify that litter arthropod community is composed by groups of species that play similar roles in ecosystem functioning, so that the increase of species richness does not translate into changes of decomposition rates. On the other hand, there are group compositions that disfavor decomposition rates. When the mite groups Laelapidae and Trombidiinae, both composed of predator species, were present, there was a decrease of litter decomposition rates. These two groups could be considered as key-species, because they could decrease the abundance of several other groups that take part on the decomposition process. Concluding, even though several species apparently play similar roles on the decomposition process, there are some key-species that influence more dramatically the ecosystem process here analyzed. / Atualmente diversos trabalhos têm investigado a relação entre biodiversidade e funcionamento dos ecossistemas. Apesar disso ainda não há uma posição conclusiva quanto ao assunto. O objetivo deste trabalho foi verificar se há relação entre a riqueza e a composição de espécies de artrópodes de serapilheira e as taxas de decomposição e liberação de nutrientes. Para isso duas hipóteses foram testadas: (i) locais com maior riqueza de espécies de artrópodes de serapilheira têm maior taxa de decomposição e de liberação de nutrientes; (ii) a composição específica da comunidade de artrópodes de serapilheira afeta a taxa de decomposição e de liberação de nutrientes. A taxa de decomposição não respondeu significativamente à riqueza de espécies de artrópodes. Esse resultado sugere que há redundância entre as espécies de artrópodes, ou seja, a comunidade de artrópode estudada provavelmente é composta por grupos de espécies que têm papéis similares, de maneira que o aumento na riqueza não se traduz em modificação no funcionamento do ecossistema. Além disso, a composição específica do grupo de ácaros Laelapidae e Trombidiidae mostrou influência negativa sobre a taxa de decomposição, o que pode ser justificado devido ao hábito alimentar que os mesmos apresentam. Nesse caso, os dois grupos de ácaros poderiam ser exemplos de grupos-chave, uma vez que sua presença implica na diminuição significativa da taxa de decomposição. Dessa maneira, conclui-se que embora a maioria das espécies apresente papéis similares, existem espécieschave que podem estar presentes, desempenhando papel importante no funcionamento dos ecossistemas.

Charles University, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical Technology Consultant: PharmDr. Ondřej Holas, Ph.D. Student: Michal Bárta Title of Thesis: Preparation of pharmaceutical nanoparticles: optimalization process Pharmaceutical, polymer nanoparticles besides others work as well as a drug carriers. Their uniqueness is not only because of their subcelular size, but as well because of the biodegradability and biocompatibility they hold. The benefit of these nanoparticiples is the possibility of creation of selective naoparticiples which are able to controle long-term release. The formulation of polymer nanoparticles can be reached within methods using preformed polymer or with polymerization of monomers. The main goal of my thesis was to optimize the production process of polymer nanoparticles and the observation of the solvent influences. The methods used for this reaserch were evaporation method and nanoprecipitation. Granulometric and electrical characteristics of particles were measured with Zetasizer ZS 90. Measurements have prooved, that it is preferable to use the nanoparticle method for the prepartion of the the small nanoparticles with low polydispersity and sufficient stability. From the results of the granulometric analysis of nanoparticles made by the...

Afin d'assurer le contrôle de son parc de production d'électricité, EDF doit maîtriser le vieillissement de ses installations pour en garantir le bon fonctionnement dans la durée. Dans ce but, il est nécessaire de disposer d’outils performants pour le modéliser et simuler la propagation des défauts dans les structures.Dans ces travaux de thèse, on s’intéresse à la propagation de fissures avec la méthode X-FEM et notamment à l’étape de localisation de la fissure par une technique de courbes de niveau. Nous avons proposé une approche fondée sur une méthode de propagation d’information de distance dite fast marching method pour rendre cette étape plus robuste. Elle est applicable à tous types de mailles,linéaires ou quadratiques.De plus, le calcul du taux de restitution d’énergie et des facteurs d’intensité de contrainte en pointe de fissure doit être suffisamment précis pour permettre de calculer la direction et l’avancée de la fissure. Dans ce but, nous avons proposé d’étudier une méthode d’intégrale de domaine pour laquelle on soulève plusieurs difficultés liées à la représentation de la fissure dans un espace tridimensionnel. Plusieurs améliorations sont proposées pour rendre les calculs plus précis et plus robustes.Dans le cas des fissures à front courbe, nous avons identifié les limites de l'utilisation des champs asymptotiques obtenus en pointe de fissure sous l'hypothèse des déformations planes comme champs auxiliaires d’une méthode d’intégrale d’interaction et nous avons proposé de nouveaux champs de déplacements auxiliaires qui prennent en compte la courbure du front de fissure. Toutes ces approches sont développées et validées dans le logiciel code_aster. / In order to ensure the control of its nuclear power plants, EDF must guarantee that they function effectively over the long term. For this purpose, it is necessary to have efficient tools tomodel and simulate crack propagation in structures. In this PhD work, we are interested in the propagation of cracks with the X-FEM method which allows using the same mesh as for a structure without default. We target especially the reconstruction of thelevel sets that characterize the position of the crack after propagation. We have proposed a fast marching method approach based on the propagation of distance information from the crack surface to the whole structure to make this step more robust in the X-FEM propagation process. It is applicable to all types of meshes, linear or quadratic. The calculation of information characteristic of thecrack status such as the energy release rate and the stress intensity factors must be accurate enough to obtain the direction and advance of the crack front ateach propagation step. For this purpose, we proposed to study a domain integral method, for which several difficulties related to the representation of the crackin a three-dimensional space are identified. Several improvements are proposed to make the calculations more accurate and more robust. In the case of curved cracks front, we have identified the limitations of using asymptotic fields obtained under the plane deformation hypothesis as auxiliary fields of an interaction integral method and we have proposed new auxiliary displacement fields that take into account the curvature of the crack front. All these methods are developed and validated with EDF software code_aster.

Submitted by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-09-21T19:19:52Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Gaya Freitas.pdf: 1529179 bytes, checksum: c9caac96378af20cf153b0fd3adead1b (MD5) / Approved for entry into archive by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-09-21T19:20:09Z (GMT) No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Gaya Freitas.pdf: 1529179 bytes, checksum: c9caac96378af20cf153b0fd3adead1b (MD5) / Made available in DSpace on 2016-09-21T19:20:09Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Gaya Freitas.pdf: 1529179 bytes, checksum: c9caac96378af20cf153b0fd3adead1b (MD5) Previous issue date: 2015-08-12 / A dapsona é uma sulfona com atividade antibiótica utilizada para doenças crônicas de pele como a psoríase, contudo seu uso pela via oral apresenta elevada incidência de eventos adversos. Uma abordagem para reduzir os efeitos colaterais é a aplicação da dapsona diretamente na área afetada, o que pode ser feito com a utilização de nanocápsulas (NC), visando aumentar a permeabilidade do fármaco na pele. Dentre os componentes que podem ser utilizados como núcleo oleoso de NC, está o óleo de arroz (Oryza sativa), devido a suas propriedades hidratantes, umectantes, antioxidantes e de proteção à radiação UV. Desta maneira, este trabalho teve por objetivo desenvolver e caracterizar NC de dapsona com diferentes polímeros - poli-ε-caprolactona (NC-P) e Eudragit® RS100 (NC-E) - utilizando diferentes quantidades de óleo de arroz e fármaco. As NC apresentaram pH levemente ácido, diâmetro de partícula inferior a 334 nm, distribuição granulométrica estreita, potencial zeta negativo (-9,9 a -33,7 mV) e eficiência de encapsulação superior a 83%. O estudo da liberação in vitro, realizado em sacos de diálise, demonstrou que as NC foram eficientes em controlar a liberação da dapsona, sendo o modelo monoexponencial o mais adequado para descrever os perfis de liberação. A nanoencapsulação diminuiu a degradação fotolítica da dapsona frente à luz UVA, obtendo-se percentuais de fármaco residual de 80,6%; 91,9% e 1,4% para NC-P1, NC-E e fármaco livre, respectivamente. Além disso, hidrogéis preparados com NC-P1 (HG-NCP1) e NC-E (HG-NCE) apresentaram pH adequado para aplicação cutânea, teor próximos a 100% e comportamento não-newtoniano pseudoplástico (HG-NCE) e plástico (HG-NCP1). Na avaliação da oclusão in vitro, observou-se que o HG-NCP1 aumentou consideravelmente a oclusão quando comparado ao HG-NCE e ao hidrogel contendo fármaco livre. Assim, estas formulações apresentam-se como sistemas promissores para aplicação cutânea de dapsona, com potencial para constituir-se em um tratamento tópico eficaz para a psoríase. / Dapsone is a sulfone with antibiotic activity used for chronic skin diseases such as psoriasis. The use of dapsone by oral route presents high incidence of adverse events. An approach to reduce side effects is the application of dapsone directly into the skin, which can be done by use of nanocapsules (NC), in order to increase the skin permeability of the drug. The rice (Oryza sativa) oil is a component that can be used as NC oil core due to its moisturizing, humectant, antioxidant and UV protection properties. Thus, this study aimed to develop and characterize dapsone-loaded NC using different polymers - poly-ε-caprolactone (NC-P) and Eudragit® RS100 (NC-E) - using different rice oil and drug concentration. The NC showed slightly acidic pH, particle diameter less than 334 nm, narrow particle size distribution, negative zeta potential (-9.9 to -33.7 mV) and encapsulation efficiency higher than 83%. The in vitro release study, carried out in dialysis bags, showed that both NC were effective in controlling the release of dapsone. The monoexponential equation was the most appropriate model to describe the release profiles. The nanoencapsulation decreases photolytic degradation of dapsone in UVA light, yielding drug remaining percentage of 80.6%, 91.9% and 1.4% for NC-P1, NC-E and free drug, respectively. In addition, hydrogels prepared with NC-P1 (HG-NCP1) and NC-E (HG-NCE) showed pH suitable for cutaneous application, content close to 100% and non-Newtonian pseudoplastic (HG-NCE) or plastic (HG-NCP1) behavior. In vitro occlusion evaluation showed that the HG-NCP1 significantly increased the occlusion factor when compared to HG-NCE and the free drug hydrogel. Thus, these formulations are promising systems for topical application of dapsone, with the potential to constitute in an effective topical treatment for psoriasis.

Submitted by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-09-22T19:30:32Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) JESSICA BRANDAO REOLON.pdf: 405938 bytes, checksum: 02d1f792d3137ced3fc728e0e11dcb3e (MD5) / Approved for entry into archive by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-09-22T19:34:00Z (GMT) No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) JESSICA BRANDAO REOLON.pdf: 405938 bytes, checksum: 02d1f792d3137ced3fc728e0e11dcb3e (MD5) / Made available in DSpace on 2016-09-22T19:34:01Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) JESSICA BRANDAO REOLON.pdf: 405938 bytes, checksum: 02d1f792d3137ced3fc728e0e11dcb3e (MD5) Previous issue date: 2016 / O herpesvírus simples (HSV) é um importante problema de saúde pública em vários países provocando ulceração genital. Dentre o arsenal terapêutico para o tratamento da infecção por HSV destaca-se o aciclovir (ACV). No entanto, este apresenta limitações no seu uso como um tempo de meia-vida curto e uma baixa solubilidade aquosa. A curcumina (CUR) é um composto natural que vem demonstrando diversas atividades terapêuticas, dentre estas a atividade antiviral, porém o seu uso por via oral também é comprometido pela baixa solubilidade em água. A encapsulação em micropartículas poliméricas (MPs) é uma abordagem farmacotécnica que podem superar as dificuldades do uso terapêutico destes dois compostos. Em vista disto, o presente trabalho visou desenvolver e caracterizar MPs pelo método de aspersão compostas por HPMC e Eudragit® RS100 como materiais poliméricos, além de manitol como adjuvante de secagem. Os resultados demonstraram que o método de preparo por aspersão (spray drying) apresentou um rendimento em torno de 50% para todas as formulações desenvolvidas, mostrando um fluxo tecnológico mais vantajoso para as partículas sem manitol. O doseamento demonstrou teores de 82 a 99% e de 81 a 94%, para ACV e CUR, respectivamente. A análise granulométrica mostrou micropartículas de tamanho micrométrico entre 8,7 e 15,3 μm. A análise morfológica evidenciou o formato esférico e confirmou o resultado das análises de tamanho. A espectroscopia na região do infravermelho mostrou uma sobreposição dos espectros obtidos pelos componentes isolados indicando boa compatibilidade entre os materiais. O perfil de liberação in vitro permitiu observar que as MPs foram capazes de controlar a liberação e melhorar a solubilidade dos compostos, destacando-se, neste quesito, as MPs compostas por HPMC. A avaliação preliminar da atividade antiviral in vitro demonstrou que a associação de ACV e CUR possui um efeito sinérgico frente ao vírus BoVH-1, sendo que as MPs foram capazes de potencializar este efeito. Neste contexto, as MPs mostraram-se sistemas promissores para a veiculação de ACV e CUR por via oral, com elevado potencial para constituir um tratamento alternativo para o herpes viral. / The herpes simplex virus (HSV), also known as human herpes virus, infects humans causing mainly genital and labial ulcerations. Among the drugs available for the treatment of HSV infection the acyclovir (ACV) is an effective antiviral drug. However this drug presents limitations in its use due to the short half-life and low water solubility. Curcumin (CUR) has demonstrated several therapeutic activities, including antiviral activity, but the oral administration of this natural compound is also compromised by low solubility. The polymeric microparticles (MP) are a pharmacotechnical approach that modifies the pharmacokinetics of the compounds and offers a possibility to overcome the difficulties of the therapeutic use. In view of this, this study aimed to develop MPs by spray drying method composed of HPMC and Eudragit® RS100 as polymeric materials, and mannitol as drying material. The results showed a yield around 50% for all developed formulations and a better technological flow rate for the particles without mannitol. The assay showed levels 82-99 and 81% to 94%, to ACV and CUR, respectively. The particle size analysis showed microparticles micrometric size between 8.7 and 15.3 micrometers. Morphological analysis showed the spherical shape and confirmed the results of size analysis. Spectroscopy in the infrared showed an overlap of the spectra obtained by the individual components indicating good compatibility between the materials. The in vitro release profile observed that the PMs were able to control the release and improved the solubility of the compounds, especially when composed of HPMC. Besides, an in vitro preliminary assessment of antiviral activity demonstrated that the combination of ACV and CUR presented a synergistic effect against BoVH-1 virus, and the MPs were able to enhance this effect. The MPs showed to be promising systems for the oral administration of ACV and CUR and could be an improved alternative treatment for viral herpes.