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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
41

Desenvolvimento de tecnologia Depot para entrega modificada de fármacos encapsulados em nanopartículas lipídicas sólidas e carreadores lipídicos nanoestruturados / Depot Technology development for drugs encapsulated in solid lipid nanoparticles and nanostructured lipid carriers delivery

Marques, Letícia Paifer, 1989- 08 September 2013 (has links)
Orientador: Francisco Benedito Teixeira Pessine / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-24T01:26:17Z (GMT). No. of bitstreams: 1 Marques_LeticiaPaifer_M.pdf: 4333961 bytes, checksum: dd287508ba192ad95556c2094f8d9d2a (MD5) Previous issue date: 2013 / Resumo: Através de modificações na estrutura química da molécula de pectina cítrica, polissacarídeo utilizado nas indústrias alimentícias como agente gelificante/espessante, foi desenvolvido um Sistema Depot para entrega subcutânea de nanopartículas lipídicas sólidas (NLS) e carreadores lipídicos nanoestruturados (CLN) contendo, respectivamente, Dexametasona (DXM) e Valerato de Betametasona (BTM). Os fármacos foram encapsulados nesses sistemas devido à necessidade de modificar seus perfis de liberação, diminuindo o número de aplicações e sua dosagem, reduzindo ocorrência de efeitos adversos. O produto da reação de oxidação da pectina cítrica foi caracterizado através de Espectroscopia da região do Infravermelho, Análise Termogravimétrica e Calorimetria Diferencial de Varredura. Os resultados indicaram o sucesso da reação, confirmado através da gelificação do hidrogel de pectina cítrica oxidada. As NLS e os CLN apresentaram valores de diâmetro médio em torno de 80nm, alta eficiência de encapsulação e perfis de liberação prolongada; para os CLN o fármaco BTM foi liberado ao longo de 144 horas e para as NLS o fármaco DXM foi liberado ao longo de 24 horas. Estes resultados mostram que as NLS de DXM poderiam ser utilizadas para tratar processos inflamatórios agudos e que os CLN de BTM seriam úteis no tratamento de processos inflamatórios crônicos / Abstract: A modified chemical structure of citrus pectin was used to develop a Depot system for subcutaneuous delivery of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) containing, respectively, Dexamethasone (DXM) and Betamethasone Valerate (BTM). Citrus pectin is a polysaccharide used in food industry as a gelling/thickener agent. The drugs were encapsulated in this system with the aim to modify their release profiles. This would result in the reduction of the number of applications and dosage. As a consequence, it would also reduce adverse side effects that these drugs may cause. The citrus pectin oxidation product was characterized by Infrared Spectroscopy, Thermogravimetric Analysis and Differential Scanning Calorimetry. The results indicated that the reaction occurred. This was confirmed by gelation of the citrus pectin oxidation product. SLN and CLN showed values with diameters around 80nm, high encapsulation efficiency and sustained release profiles. BTM was released from the CLN over 144 hours and DXM was released from the NLS over 24 hours. These results showed that the DXM-NLS would be useful in the treatment of acute inflammatory processes. BTM-CLN could be applied in the treatment of chronic inflammatory processes / Mestrado / Físico-Química / Mestra em Química
42

Desenvolvimento de nanopartículas lipídicas para o carreamento conjunto do gene para PTEN e mitoxantrona em células de câncer de mama e de próstata / Development of lipidic nanoparticles for PTEN gene and mitoxantrone delivery in breast and prostate cancer cells

Radaic, Allan, 1986- 21 August 2018 (has links)
Orientadores: Eneida de Paula, Marcelo Bispo de Jesus / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-21T18:01:25Z (GMT). No. of bitstreams: 1 Radaic_Allan_M.pdf: 4265854 bytes, checksum: c076b4c5a6bc95bdcef69dea768f492f (MD5) Previous issue date: 2012 / Resumo: O câncer é a doença genética responsável pelo maior número de mortes em países desenvolvidos e a segunda maior causa mortis em países em desenvolvimento. Uma das principais formas de tratamento do câncer é a quimioterapia, que se utiliza de fármacos para induzir a morte em células cancerígenas, impedindo, assim, seu crescimento anormal. Para ultrapassar desvantagens das tratamentos atuais, novas terapias vêm sendo desenvolvidas. Dentre elas, a terapia gênica e o uso de sistemas de liberação de fármacos foram as abordagens escolhidas em nossa pesquisa. Carreadores Lipídicos Nanoestruturados (CLN) e Nanopartículas Lipídicas Sólidas (NLS) são alternativas interessantes para viabilizar tais terapias, por conseguirem entregar material genético de forma efetiva e segura de genes, fármacos e proteínas em células alvo. Portanto, esta dissertação teve por objetivos i) desenvolver e aperfeiçoar um novo método de produção de CLN e NLS: a extrusão de microemulsão e ii) produzir nanopartículas capazes de carrear genes (gene codificante para PTEN) e fármacos (mitoxantrona) concomitantemente em células de câncer. Os resultados demonstram que a extrusão de microemulsão é um método factível para a produção de tais partículas, sendo que 15 passagens pela membrana de 100 nm, 5 ºC acima da temperatura de fusão dos lipídios sólidos são os melhores parâmetros para otimização deste processo. As nanopartículas lipídicas produzidas apresentaram diâmetro médio em torno de 140 nm e foram estáveis por, pelo menos, 180 dias estocadas a 4 ºC. Além disso, CLN e NLS mostraram-se semelhantes quanto ao tamanho, potencial Zeta e polidispersão (PDI). Apesar de não apresentarem diferenças quanto a transição de fase, as nanopartículas lipídicas apresentaram uma ultraestrutura monolítica bastante distinta dos lipossomas, o que garantiu uma alta eficiência de encapsulamento para o fármaco mitoxantrona: de 81% em CLN e 64 % em NLS. Finalmente, o carreamento concomitante do fármaco mitoxantrona e do gene da PTEN diminuiu a viabilidade celular em linhagens de câncer de mama (MCF-7) e de próstata (PC3), de maneira mais eficiente que formulações lipossomais / Abstract: Cancer is the genetic disease responsible for major death causes in developed countries and it is the second leading cause of death in developing countries. One of the main forms of cancer treatment is chemotherapy, which uses drugs to induce death in neoplastic cells, thereby preventing their overgrowth. To overcome disadvantages of current treatments, new therapies have been developed. Among them, gene therapy and the use of drug delivery systems were the approaches used in our research. Nanostructured Lipid Carriers (NLC) and Solid Lipid Nanoparticles (SLN) are suitable carriers for such therapies since they can effectively and safely deliver genetic material, drugs and proteins in target cells. Therefore, this work was aimed i) to develop and optimize a new method of production of NLC and SLN: the microemulsion extrusion and ii) to produce nanoparticles capable of co-delivery genes (the coding gene for PTEN) and drugs (mitoxantrone) into cancer cells. The results demonstrate that microemulsion extrusion is a reliable method for the production of such particles, being 15 passages through 100 nm membrane, at 5 °C above the solid lipid melting temperature, are the best parameters for process optimization. The lipid nanoparticles showed average diameter of 140 nm and they were stable up to 180 days of storage at 4 °C. Moreover, NLC and SLN showed similar size, Zeta potential and polydispersity (PDI). While calorimetry did not reveal great differences among the formulations tested, transmission electron microscopy revealed a monolithic structure for lipid nanoparticles distinct from lipossomes, which allowed NLC and SLN to encapsulate 81 and 64 %, respectively, of mitoxantrone. Finally, concomitant entrapment of mitoxantrone and PTEN gene in lipid nanoparticles led to a decrease in the cell viability of breast (MCF-7) and prostate (PC3) cancer cells, more efficiently than liposomal formulations / Mestrado / Bioquimica / Mestre em Biologia Funcional e Molecular
43

Assemblage nanoparticules lipidiques solides-polysaccharide : étude des propriétés physico-chimiques pour la vectorisation d’un polyphénol / Solid lipid nanoparticles-polysaccharide assembling : study of physicochemical properties for the vectorization of a polyphenol

Hajjali, Hassan 16 December 2015 (has links)
Ce travail porte sur la conception d'un système lipo-polysaccharidique sous forme d'un assemblage de taille micrométrique entre des nanoparticules lipidiques solides (SLNs) et un biopolymère. Le but est de formuler un vecteur pouvant : transporter un principe actif hydrophobe, résister aux conditions gastriques, et permettre un relargage contrôlé en conditions spécifiques. Le choix de la molécule active s'est porté sur un polyphénol, la curcumine, pour ses activités anti-oxydantes et anti-inflammatoires. Etant hydrophobe, la curcumine a été encapsulée dans des nanoparticules de beurre de karité qui est un lipide d'origine naturelle et solide à température ambiante. Les systèmes lipidiques ne résistant pas aux conditions gastriques, les nanoparticules ont été incluses dans une matrice de chitosane sous forme d'un assemblage micrométrique contrôlé par des interactions électrostatiques. Ce polymère naturel, chargé positivement grâce à la présence de groupements amines, résiste aux attaque des enzymes gastriques et présente des interactions spécifiques avec la muqueuse intestinale et notamment les mucines permettant ainsi un ciblage vers l'intestin et le côlon. La première partie de cette étude est focalisée sur le système beurre de karité-curcumine en absence de chitosane. L'effet du polyphénol sur la cristallisation du lipide a tout d'abord été étudié. L'influence de la composition du mélange ternaire (beurre de karité, tensioactif, eau) sur les propriétés des nanoparticules formées a ensuite été étudiée en utilisant la méthodologie des plans de mélanges. Cela a permis de contrôler la taille des SLNs formulées et de mettre ensuite en évidence l'influence de la taille des particules sur le taux d'encapsulation de la curcumine. La seconde partie est axée sur l'assemblage entre les nanoparticules et le chitosane. Des particules micrométriques ont ainsi été obtenues par interactions électrostatiques entre les SLNs encapsulant la curcumine et stabilisées par des phospholipides et le chitosane / This work deals with the design of a lipo-polysaccharidic system as a micrometric assembly between solid lipid nanoparticles (SLNs) and a biopolymer. The aim is to formulate a vector can: carry a hydrophobic active molecule, resist to gastric conditions, and allow a controlled release in specific conditions. Choosing the active molecule is carried on a polyphenol, curcumin, for its antioxidant and anti-inflammatory activities. Being hydrophobic, curcumin was encapsulated in shea butter nanoparticles, which is a natural lipid and solid at room temperature. Lipid nanocarriers are not resistant to gastric conditions; the nanoparticles have been included in a chitosan matrix in the form of a micrometric assembly controlled by electrostatic interactions. This natural polymer, positively charged due to the presence of amine groups, is resistant to attack by gastric enzymes and has specific interaction with the intestinal mucosa and in particular the mucin which can be useful as a carrier for curcumin in colon targeted drug delivery. The first part of this study focused on shea butter–curcumin system with the absence of chitosan. The effect of polyphenols on the lipid crystallization was studied. The influence of the composition of the ternary mixture (shea butter, surfactant, water) on the properties of the nanoparticles was then investigated by using the response surface methodology. This helped to control the size of SLNs and then to show the influence of particle size on the encapsulation efficiency of curcumin. The second part focuses on the assembling between the nanoparticles and chitosan. Micrometric particles were obtained through electrostatic interactions between SLNs encapsulated curcumin and chitosan
44

Desenvolvimento de nanopartículas como sistema carreador para os fungicidas carbendazim e tebuconazole visando aplicações em agricultura / Development of nanoparticles as carrier system for carbendazim and tebuconazole fungicides aiming applications in agriculture

Campos, Estefânia Vangelie Ramos, 1989- 02 February 2015 (has links)
Orientador: Leonardo Fernandes Fraceto / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-26T15:38:39Z (GMT). No. of bitstreams: 1 Campos_EstefaniaVangelieRamos_M.pdf: 7315526 bytes, checksum: e92d25c76302901307a5c47fb9437573 (MD5) Previous issue date: 2015 / Resumo: O Brasil tornou-se um dos maiores consumidores de defensivos agrícolas em função do seu crescimento no cenário mundial na produção agrícola. Embora esses produtos tragam benefícios para a produção agrícola, têm sido encontrados em concentrações alarmantes nos recursos hídricos e no solo, levando a necessidade de se buscarem alternativas para a redução de seus impactos negativos no meio ambiente. O presente trabalho teve como objetivo o preparo e caracterização de nanopartículas poliméricas (NC) e lipídicas sólidas (NLS) para o carreamento conjunto dos fungicidas carbendazim (MBC) e tebuconazol (TBZ), a fim de aumentar a sua eficácia biológica, além de diminuir os processos físico-químicos de degradação que estes ativos sofrem no ambiente. Os dois sistemas carreadores preparados apresentaram alta eficiência de encapsulação para ambos os fungicidas, superior a 99 %. As NC contendo fungicidas apresentaram diâmetro médio em torno de 550 nm, índice de polidispersão inferior a 0,2 e potencial zeta de aproximadamente -17 mV. Enquanto as NLS apresentaram diâmetro médio em torno de 270 nm, índice de polidispersão superior a 0,2 desde o tempo inicial e potencial zeta de -20 mV. As nanopartículas foram capazes modificar o perfil de liberação dos fungicidas. A liberação do MBC quando associado as nanopartículas em 6 dias foi em torno de 30 % Já para o TBZ no mesmo período de tempo a liberação a partir das nanopartículas foi de 50 %. O modelo matemático que mais se ajustou a liberação do MBC de ambas as nanopartículas foi o de Higuchi. Considerando a liberação do TBZ a partir das nanopartículas o modelo de primeira ordem melhor se ajustou. Os ensaios de liberação em solo demonstrou que as nanopartículas reduzem a porcentagem de lixiviação dos fungicidas, onde para o MBC houve liberação de 17 % a partir da formulação comercial e quando associado as nanopartículas esse valor foi inferior a 5 % com um total de 10 lavagens do solo. Já para o TBZ a formulação comercial liberou 20 % e quando associado as nanopartículas foi em torno de 15 %. Ensaios de viabilidade celular demostraram que as partículas diminuem a toxicidade dos fungicidas à célula animal , sendo os valores de IC50 de 67, 89 e 81 µg/mL para a formulação comercial, NC e SLN respectivamente. Ensaios na espécie P. vulgaris evidenciaram que os fungicidas quando encapsulados causam menos impactos no desenvolvimento das plântulas. Os resultados obtidos mostraram que foi possível preparar sistemas carreadores para os fungicidas sendo, desta forma, obtidos bons sistemas carreadores com modificação no perfil de liberação e diminuição da citotoxicidade, desta forma sendo uma alternativa para o combate de pragas que acometem as culturas na agricultura / Abstract: Brazil has become a major consumer of pesticides according to their growth on the world stage in agricultural production. Although these products bring benefits to agriculture, they cause many impacts to the environment because they are found in high concentrations in soil and water resources. This work aimed to prepare and characterize nanoparticles (polymeric and solid lipid) in order to encapsulate two fungicides carbendazim and tebuconazole. This strategy aims to minimize their impacts to the environment and increase their biological effectiveness, besides of decreasing the physicochemical process of degradation of these compounds into the environment. Both carrier systems showed high encapsulation efficiency for both fungicides (higher than 99 %). The polymeric nanocapsules (NC) with fungicides showed mean diameter around 550 nm, polidispersity lower than 0.2 and zeta potential around - 17 mV. While solid lipid nanoparticles (NLS) showed mean diameter around 270 nm, polidispersity higher than 0.2 since initial time and potential zeta around - 20 mV. Nanoparticles were able to modify the release profile of fungicides. The release of the MBC when associated nanoparticles in 6 days was around 30%. For the TBZ in the same period of time the release from the nanoparticles was 50%. The mathematical model that most adjusted the release of MBC of both nanoparticles was to Higuchi. Whereas the release of the nanoparticles from the TBZ model best fit was observed by the first-order. Cell viability assays showed that particles decrease the toxicity of fungicides, which IC50 values of 67, 89 and 81 µg/mL for the commercial formulation, NC and SLN respectively. The plant assays with P. vulgaris showed that fungicides when encapsulated provoke less impact on seedling development in relation to commercial formulation. The results obtained with these formulations showed that it was possible to prepare nanoparticlescarrier systems for both fungicides in the same carrier and that the fungicide encapsulation decreased the cytotoxicity, increase fungicides effectiveness and thus being a possible alternative to control diseases that affect crops in agriculture / Mestrado / Bioquimica / Mestra em Biologia Funcional e Molecular
45

Formulation et caractérisation de particules lipidiques submicroniques encapsulant des filtres ultraviolets organiques et inorganiques / Formulation and characterization of submicronic lipid particles encapsulating organic and inorganic UV filters

Gilbert, Elodie 16 December 2015 (has links)
Les écrans solaires sont des formulations dont l’application permet de protéger la peau des effets néfastes du rayonnement ultraviolet (UV) et notamment de l’apparition des cancers cutanés. Ces formulations contiennent des filtres UV organiques et/ou inorganiques. Certains filtres UV organiques sont connus pour pénétrer la peau et engendrer des réactions allergiques et photo-allergiques. De plus, certains d’entre eux peuvent engendrer des effets toxiques sur les cellules cutanées vivantes et atteindre la circulation systémique. Les filtres UV inorganiques sont la plupart du temps incorporés dans les écrans solaires sous forme de nanoparticules afin d’améliorer les qualités esthétiques des écrans solaires minéraux. Les nanoparticules utilisées comme filtres UV inorganiques exerceraient des effets toxiques sur les cellules nucléées de la peau. Les nanoparticules et nanocapsules lipidiques sont des particules lipidiques submicroniques intéressantes pour formuler les actifs pharmaceutiques et cosmétiques et notamment les filtres UV. L’objectif de ce travail était de développer des suspensions de nanoparticules lipidiques pour formuler des filtres UV inorganiques et organiques en les maintenant à la surface de la peau tout en augmentant leur efficacité photo-protectrice. Ces travaux ont permis de développer des suspensions de nanoparticules lipidiques encapsulant des filtres UV inorganiques en augmentant leur pouvoir photo-protecteur. Cette étude a également mis en évidence l’intérêt de ces suspensions de nanoparticules lipidiques pour encapsuler un filtre UV organique et limiter sa perméation percutanée tout en augmentant son efficacité filtrante dans le domaine UV / Sunscreens are topical formulations that protect the skin against damages induced by ultraviolet (UV) radiations and notably skin cancers formation. Those formulations contain organic and/or inorganic UV filters. Some organic UV filters are known to penetrate the skin and trigger allergic and photo-allergic cutaneous reactions. Moreover, some of them are responsible for toxic effects on skin nucleated cells and could reach systemic circulation. Nanoparticles of inorganic UV filters are often incorporated into sunscreens to improve their aesthetic qualities. Nanoparticles used as inorganic UV filters could exercise toxic effects on skin nucleated cells. Lipid nanoparticles and nanocapsules are submicronic lipid particles interesting to formulate pharmaceutical and cosmetic active compounds and notably UV filters. The aim of this work was to develop lipid nanoparticles to entrap organic and inorganic UV filters maintaining them at skin surface while increasing their photo-protection efficiency. This study permitted to develop lipid nanoparticle suspensions entrapping inorganic UV filters enhancing their photo-protection efficiency. This work also highlighted the interest of these lipid nanoparticle suspensions to entrap an organic UV filter avoiding its percutaneous permeation while enhancing its photo-protection efficiency
46

Development, Characterization and Evaluation of Solid Lipid Nanoparticles as a Potential Anticancer Drug Delivery System

Patel, Meghavi January 2012 (has links)
No description available.
47

Influência de micro e nanopartículas lipídicas sólidas na eficácia de formulações fotoprotetoras bioativas / Influence of solid lipid micro and nanoparticles on the efficacy of bioactive photoprotective formulations

Martins, Rodrigo Molina 22 April 2014 (has links)
O presente trabalho teve o objetivo de desenvolver uma formulação tópica contendo os filtros solares benzofenona-3 e avobenzona microencapsulados em associação com filtro solar não encapsulado octocrileno e nanoparticulas lipídicas sólidas contendo rutina (formulação completa) e avaliar a eficácia fotoquimiopreventiva dessa formulação usando biópsias de pele humana e pele reconstruída in vitro. Microparticulas lipídicas sólidas contendo grandes quantidades de filtros solares, benzofenona-3 e avobenzona foram obtidas pela técnica do spray congealing com propriedades adequadas para aplicação tópica. Além disso, o processo de microencapsulação foi capaz de diminuir a penetração de benzofenona-3 na pele, aumentar a estabilidade da avobenzona frente à radiação ultravioleta A e a capacidade fotoprotetora desses filtros microencapsulados em formulações tópicas quando expostos a radiação ultravioleta. Nanopartículas lipídicas sólidas contendo o flavonóide rutina foram produzidas pelo processo de homogeneização a alta pressão e suas condições foram otimizadas pelo método da desejabilidade rendendo nanopartículas lipídicas sólidas com tamanho médio de 74,22 ±2,77 nm, índice de polispersividade de 0,161±0,03 e eficiência de encapsulação de 98,90 ±0,25 %. Em adição, as nanopartículas mostraram serem capazes de proteger a viabilidade celular de fibroblastos de ratos L929 irradiados com radiação ultravioleta A e B. Para a eficácia fotoquimiopreventiva a formulação completa foi capaz de evitar/diminuir a formação de células apoptóticas, caspase-3, dímeros de ciclobutanodipirimidina, metaloproteinases e peroxidação lipídica em pele humana e pele reconstruída expostos a UVB. O processo tecnológico de microencapsulação e nanoencapsulação dos ativos avaliados mostrou ser eficaz, não comprometendo as propriedades de fotoproteção dos filtros solares e rutina, apresentando resultados similares ou melhores do que as formulações contendo os ativos na forma livre. Portanto, o desenvolvimento de formulações contendo ativos microencapsulados e nanoencapsulados é uma alternativa interessante para o emprego em produtos comerciais para proteção solar, por diminuir as características indesejáveis como penetração e instabilidade, melhorando as propriedades fotoprotetoras e evitando a necessidade de desenvolver novos compostos com propriedades fotoprotetoras. / This study aimed the pharmaceutical development of a topical formulation containing an association of microencapsulated sunscreens benzophenone-3 and avobenzone, free sunscreen octocrylene and rutin flavonol solid lipid nanoparticles (complete formulation). This formulation was assessed for photochemoprotective ability using human skin obtained surgically and reconstructed human skin. Solid lipid microparticles containing large amounts of sunscreens benzophenone-3 and avobenzone were obtained by the spray congealing technique under conditions that allowed the manufacture of microparticles with suitable properties for topical application. The microencapsulation conditions were also able to reduce the penetration of benzophenone-3 through the skin, enhanced the stability of avobenzone against the ultraviolet radiation (UVR) and increased the photoprotective ability of both filters in topical formulations exposed to UVR. Solid lipid nanoparticles containing rutin were produced by the high pressure homogenization process whose conditions were optimized using the desirability method, yielding nanoparticles with size of 74.22 ± 2.77 nm, polispersivity index of 0.161 ± 0.03 and encapsulation efficiency of 98.90 ± 0.25%. In addition, the nanoparticles were able to avoid the death of L929 mice fibroblasts exposed to UVR A and B. For the photochemopreventive ability studies, the complete formulation was able to reduce/avoid the induction of apoptotic cells, caspase-3, CPDs, metalloproteinases and lipid peroxides in human skin obtained surgically and reconstructed human skin in vitro exposed to UVB.Thus, the micro and nanoencapsulation solved some intrinsic problems related to sunscreens and rutin without, however, compromising their photohemoprotective ability, since the results showed similar or better efficacy when compared to the formulations containing actives in free form. Therefore, the development of formulations containing microencapsulated and nanoencapsulated compounds is an interesting alternative for employment in commercial products for sun protection by decreasing the undesirable characteristics, such as penetration and instability, improving the photoprotective properties and avoiding the need to develop new compounds with photoprotective characteristics.
48

DESENVOLVIMENTO E CARACTERIZAÇÃO DE NANOPARTÍCULAS LIPÍDICAS CONTENDO HALCINONIDA PARA MODULAÇÃO DA INFLAMAÇÃO NO PROCESSO DE CICATRIZAÇÃO DE LESÕES CUTÂNEAS

Lopes, Clarissa Elize 21 December 2015 (has links)
Made available in DSpace on 2017-07-21T14:13:05Z (GMT). No. of bitstreams: 1 Clarissa Elize.pdf: 4457240 bytes, checksum: d8f2520757eb456c2ae4c01f7a1f0343 (MD5) Previous issue date: 2015-12-21 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Skin wounds are interruptions of the normal physiological and anatomical structure of the skin causing damage by loss of barrier function becoming the organism exposed to various types of substances and microorganisms. A fast healing of the wound is essential to avoid the risk of infections and other complications. The aim of this work was to the development of lipid nanoparticles, as solid lipid nanoparticles and lipid-core polymeric nanoparticles containing halcinonide to modulate the inflammatory phase of wound healing, reducing pain, discomfort, edema, exudates and to reduced the drug toxicity. To this end, nanoparticles were obtained and characterized for particle size, physicochemical properties, stability, encapsulation efficiency, scanning electron microscopy by field emission, x-ray diffraction, spectroscopy in the infrared and Raman Fourier Transform, differential scanning calorimetry, thermal gravimetric analysis, study of the in vitro skin permeation and in vivo evaluation of the inflammatory response and drug toxicity. Furthermore, a highperformance liquid chromatography method for quantification of the drug was developed and validated. Nanoparticles had an average diameter ranging from 260-500 nm, polydispersity index below 0.37, zeta potential close to -30 mV, pH between 5.3 and 6.5 and were stability after storage for 60 days. The microscopy images showed spherical shape with smooth surface. The X-ray diffraction analysis showed drug amorphization in the nanostructured systems. By infrared and Raman spectroscopy was identified the characteristic bands of main components of the formulations, indicating no chemical bonding between them. Thermal analysis revealed the melting peaks of the drug and lipids and polymer and the temperature of its degradation. Nanoparticles showed 5.0% of drug permeation in 24 hours. In vivo study showed that the pure halcinonide was toxic; producing systemic adverse effects and nanoparticles containing the drug was able to modulate the inflammation healing, avoiding the edema and exudates formation and however impairing the subsequent stages of the healing process. However, the incorporation of the halcinonide in nanoparticles was able to reduce the drug toxicity due to the control of the drug release. Regarding the samples of lipid nanoparticles, both showed similar results, wherein the lipid-core polymeric nanoparticles showed better retraction of the wound and macroscopic appearance, possibly due to the polymer control associated with the lipid in halcinonide release. / Lesões cutânea são interrupções da sua estrutura anatômica normal e fisiológica que causam danos pela perda da função barreira da pele tornando-a exposta a diversos tipos de substâncias e microrganismos. Dessa forma uma rápida cicatrização desta lesão é fundamental para evitar o risco de infecções e outras complicações. O objetivo deste trabalho foi o desenvolvimento de nanopartículas lipídicas, na forma de nanopartículas lipídicas sólidas e nanopartículas poliméricas de núcleo lipídico, para veiculação de halcinonida para modulação da fase inflamatória da cicatrização, reduzindo dor, desconforto, edema e exsudato, aliado a redução da toxicidade do fármaco. Para tanto, as nanopartículas foram obtidas e caracterizadas quanto ao tamanho de partícula, propriedades físico-químicas, estabilidade, eficiência de encapsulação do fármaco, microscopia eletrônica de varredura por emissão de campo, difração de raios x, espectroscopia na região do infravermelho e Raman com Transformada de Fourier, calorimetria diferencial de varredura, análise termogravimétrica, estudo de permeação cutânea in vitro e avaliação in vivo da resposta inflamatória e da toxicidade do fármaco. Além disso, um método para quantificação do fármaco por cromatografia líquida de alta eficiência foi desenvolvido e validado. As nanopartículas apresentaram diâmetro médio variando entre 260 a 500 nm, índice de polidispersão abaixo de 0,37, potencial zeta próximo a -30 mV, pH entre 5,3 e 6,5 e apresentaram estabilidade após armazenamento de 60 dias. As imagens obtidas por microscopia revelaram formato esférico com superfície lisa. A análise de difração de raios x demonstrou a amorfização do fármaco nos sistemas nanoestruturados. Por espectroscopia na região do infravermelho e Raman puderam-se identificar as bandas características dos principais componentes das formulações, indicando que não houve ligação química entre eles. A análise térmica revelou os picos da fusão do fármaco e dos lipídeos e polímero utilizados e a temperatura da sua degradação. As nanopartículas apresentaram 5,0 % do fármaco permeado em 24 horas de estudo. O estudo in vivo revelou que a halcinonida livre foi tóxica, produzindo efeitos adversos sistêmicos e as nanopartículas contendo o fármaco foram capazes de modular a inflamação da cicatrização, evitando a formação de edema e exsudato, porém prejudicando as fases subsequentes do processo de cicatrização. No entanto, a incorporação da halcinonida nas nanopartículas foi capaz de reduzir a toxicidade do fármaco pelo controle da sua liberação. Em relação às amostras, as duas nanopartículas desenvolvidas apresentaram resultados semelhantes,sendo que as nanopartículas poliméricas de núcleo lipídico mostrou melhor retração da ferida e aspecto macroscópico, possivelmente pelo controle polimérico associado ao do lipídeo para liberação da halcinonida.
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Designing Stimuli-Responsive Porous Silica Materials using Solid Lipid Nanoparticles (SLN) and Magneto-responsive Surfactants for Delivery of Curcumin / Conception de matériaux poreux silicatés stimuli-responsive en utilisant des nanoparticules lipidiques solides (SLN) et tensioactifs magnétiques pour la vectorisation de la curcumine

Kim, Sanghoon 28 October 2015 (has links)
Ce travail a consisté à préparer des matériaux silicatés poreux à caractère stimuli-sensible à base de nanoparticules lipidiques solides (SLN) et de tensioactifs magnétiques. Plusieurs systèmes à base de tensioactifs ont été utilisés afin de synthétiser des matériaux silicatés à porosité contrôlée en utilisant des méthodes décrites dans la littérature ou mises au point au laboratoire. De différents caractères stimuli-sensible ont été introduits dans les matériaux silicatés poreux en fonction de système utilisé: les nanoparticules lipidiques solides (SLN) pour les matériaux sensible au pH et les tensioactifs magnétiques pour les matériaux sensible au champ magnétique. Premièrement, les matériaux à base de nanoparticules lipidiques solides (SLN) ont été utilisés pour la vectorisation d’un principe actif, la curcumine. La libération de la curcumine a été contrôlée en fonction de pH. Un revêtement sur la surface silice a été également employé pour mieux contrôler la libération de la curcumine. D’autre part, la sensibilité au champ magnétique a été introduite dans des silices mésoporeuses en utilisant des tensioactifs magnétiques. Leurs propriétés d’auto-assemblage (i.e. micelles, vésicules) ont été mise en évidence. Ainsi, la synthèse de matériaux silicatés poreux à caractère magnétique-sensible a été effectuées en utilisant ces tensioactifs. Enfin, les SLN magnétiques ont été préparés en combinant les SLN avec un tensioactif magnétique, qui ont été servi pour la synthèse de catalyseur à base de la silice méso-macroporeuse dopée en nanoparticules d’oxyde de fer / This work is to prepare stimuli-responsive porous silica materials based on solid lipid nanoparticles (SLN) and magnetic surfactants. To develop this study, several surfactants systems were used to synthesize silica materials with controlled porosity via protocols described in the literature or developed in the laboratory. Different stimuli-responsive characters were introduced in porous silica materials as a function of system used: solid lipid nanoparticles (SLN) for pH-sensitive and magnetic-sensitive surfactants for magnetic silica materials. First, the materials synthesized with solid lipid nanoparticles (SLN) were used for the delivery of an anti-carcinogenic drug, curcumin. A coating method on silica surface was also used to better control the release of curcumin. Secondly, the responsiveness to the magnetic field was introduced in silica materials using the magnetic surfactants. Their self-assembly properties (i.e. micelles, vesicles) were studied and their applications in the synthesis of magnetic porous silica materials were investigated. Finally, the magnetic solid lipid nanoparticles have been prepared by combining SLN with magnetic surfactants, which have been used for the synthesis of meso-macroporous silica catalyst encapsulating iron oxide nanoparticles.
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Nanopartículas lipídicas sólidas contendo genisteína para uso tópico

Silva, Lorena Maione 28 February 2012 (has links)
Submitted by Cássia Santos (cassia.bcufg@gmail.com) on 2014-09-09T11:45:33Z No. of bitstreams: 2 Dissertacao_Lorena_Maione_Silva_Ciencias_Farmaceuticas.pdf: 516603 bytes, checksum: ec25498f249629c65bc31a3ef2bd8588 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2014-09-09T11:45:33Z (GMT). No. of bitstreams: 2 Dissertacao_Lorena_Maione_Silva_Ciencias_Farmaceuticas.pdf: 516603 bytes, checksum: ec25498f249629c65bc31a3ef2bd8588 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2012-02-28 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Genistein (GEN), isoflavone contained in soybeans, shows activity against a large number of cancers, including skin cancer. However, to be used topically it is essential the association of GEN in an appropriate formulation. The aim of this study was the development and characterization of solid lipid nanoparticles (SLN) contends genistein for topical application. A bioanalytical method was developed and validated for GEN quantification in skin layers with High Performance Liquid Chromatographer (HPLC) with UV detection. The SLN was obtained with glyceryl behenate, polysorbate 80, sorbitan trioleate and different amounts of cetylpyridinium chloride (CPC) (0.5 - 0.05%). The characteristics in terms of particle size, size distribution, zeta potential, entrapment efficiency and drug recovery were evaluated. In vitro release, passive and iontophoretic, skin permeation studies were performed. Cytotoxicity studies were carried out in melanoma cells (B16F10) with free drug and SLN with and without GEN. The analytical method was linear in the concentration range of 0.1 to 60 mg/mL. Limit of quantification was 100 ng/mL for both skin layers. Recovery of the drug ranged from 95.57 to 97.57%. The method was able to analyze the GEN without suffering interference from endogenous skin components. SLN loaded with GEN showed positive surface (+ 23 mV) and average size of 343 nm. Particles were obtained with high entrapment efficiency (93%) and drug load was 5.45%. In vitro release studies demonstrated that the release of GEN from SLN occurs in two stages with a large amount of drug released within the first six hours, followed by a slow release of the remaining drug in the lipid matrix of SLN in the following hours. When administered in the skin, during in vitro passive permeation studies, the SLN increased retention of GEN in stratum corneum and remaining skin compared with free GEN. After iontophoresis application in formulation of SLN containing GEN thirteen times more GEN was retained on stratum corneum and three times more drug was retained on remaining skin. In cellular cytotoxicity studies SLN favored the increase of interaction of drug with the cells and the cytotoxicity was concentration-dependent. Thus, GEN loaded SLN increased drug skin permeation and retention and shows to be a potential formulation for topical application. / A genisteína (GEN), isoflavona contida nos grãos da soja, apresenta atividade contra um grande número de tipos de câncer, incluindo o câncer de pele. No entanto, para ser usada topicamente é fundamental que a GEN esteja associada a uma formulação adequada. O objetivo deste trabalho foi desenvolver e caracterizar nanopartículas lipídicas sólidas (NLS) contendo genisteína para aplicação tópica. Para a quantificação da genisteína nas diferentes camadas da pele foi desenvolvida e validada uma metodologia bioanalítica em cromatografia líquida de alta eficiência (CLAE) com detecção no UV. As NLS foram obtidas com behenato de glicerila, polissorbato 80, trioleato de sorbitano e tensoativo catiônico cloreto de cetilpiridínio (CPC) em diferentes quantidades (0,5 – 0,05%). As NLS foram caracterizadas quanto ao tamanho, PdI, potencial zeta, eficiência de encapsulação e recuperação. Foram realizados estudos in vitro de liberação e permeação cutânea passiva e iontoforética. Estudos de citotoxicidade foram realizados em linhagem de melanoma (B16F10) com fármaco livre e NLS com e sem GEN. O método de quantificação do fármaco mostrou-se linear na faixa de concentração de 0,1 a 60 μg/mL. O limite de quantificação foi de 100 ng/mL para ambas as camadas da pele. A recuperação do fármaco variou entre 95,57 a 97,57%. Ainda, o método foi capaz de analisar a GEN sem sofrer interferência dos componentes endógenos da pele. As NLS carregadas com fármaco apresentaram carga superficial positiva (+ 23 mV) e tamanho médio de 343 nm. Também foram obtidas partículas com alta eficiência de encapsulação (93%) e carga de fármaco de 5,45%. Os estudos de liberação in vitro demonstraram que a liberação da GEN a partir das NLS ocorre em duas fases, com uma grande quantidade de fármaco liberada nas seis primeiras horas, seguida por uma liberação lenta do restante do fármaco da matriz lipídica das NLS nas horas seguintes. Quando administrada na pele, nos estudos de permeação passiva in vitro, as NLS aumentaram a retenção da GEN tanto no estrato córneo quanto na pele remanescente em comparação à administração da GEN livre. Após a aplicação da iontoforese na formulação de NLS contendo GEN, treze vezes mais GEN ficou retida no EC e três vezes mais fármaco ficou retido na pele remanescente. Nos estudos de citotoxicidade, as NLS favoreceram o aumento da interação do fármaco com as células e a citotoxicidade foi concentração-dependente. Deste modo, a encapsulação da GEN em NLS aumentou a permeação e retenção do fármaco na pele, demonstrando assim, potencial para aplicação tópica.

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