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"November 2004" / Bibliography: leaves 149-179. / xxviii, 218 leaves : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / "This study addresses exposure during spraying of malathion and fenthion insecticides for fruit fly control and hexamethylene di-isocyanate (HDI)-based paint in the automotive and furniture industries. The research aims to characterize exposures and symptoms, and assess the adequacy of personal protective equipment under field conditions." --p. iii. / Thesis (Ph.D.)--University of Adelaide, Faculty of Health Sciences, Dept. of Public Health, 2005

Orientador: Maria Virgínia Costa Scarpa / Banca: Maria Valéria Robles Velasco / Banca: Marcos Antônio Corrêa / Resumo: A mistura de óleo, água e tensoativo é capaz de formar estruturas e sistemas variados, dependendo das características e da proporção dos componentes utilizados. Sistemas microestruturados, como cristais líquidos e microemulsões, são utilizados para encapsular fármacos e substâncias ativas em produtos farmacêuticos e cosméticos. O objetivo desse trabalho foi desenvolver sistemas microestruturados para a incorporação da cafeína com finalidade de uso tópico para otimizar o tratamento da hidrolipodistrofia ginóide. A mistura direta de PPG-5-Ceteth-20 (tensoativo), adipato de dibutila (fase oleosa) e água em diferentes proporções possibilitou a obtenção de formulações com formas de estruturação variadas, como microemulsão, emulsão e mesofases líquido-cristalinas. As formulações obtidas foram caracterizadas por meio de microscopia de luz polarizada, determinação de índice de refração, densidade relativa e condutividade e comportamento reológico. Estudos de solubilidade mostraram que os sistemas foram capazes de solubilizar cerca de 1,5% de cafeína. Estudos de liberação in vitro, que utilizaram modelo de célula de difusão em sistema estático do tipo Franz adaptada ao equipamento de dissolução indicaram que as formulações apresentaram características de sistemas reservatórios de liberação prolongada. Para o estudo de permeação in vivo foram utilizados suínos machos, Landrace x Large White, submetidos ao tratamento com formulação acrescida ou não de cafeína. Fragmentos de pele e hipoderme foram retirados para a análise histológica. A formulação com características de cristal líquido de fase hexagonal foi eficaz em aumentar a permeação cutânea à cafeína, facilitando assim sua ação. A cafeína aplicada desta forma fez com que houvesse uma redução significativa da espessura da hipoderme. O sistema atua como promotor de permeação e garante a eficácia da cafeína no tratamento da celulite. / Abstract: Oil, water and surfactant mixture may form a variety of structures and phases accordingly to the characteristics and the ratio of the used components. Microcompartmented systems as liquid crystals and microemulsions are used to encapsulated drugs and active substances in pharmaceutical and cosmetic products. The objective of this research was the development of microcompartmented systems for incorporation of caffeine with the purpose of topical use on treatment of the gynoid lipodystrophy. The direct mixture of PPG-5-Ceteth-20 (surfactant), dybutyl adipate (oil phase) and water in differents proportions made possible to obtain formulations with different structuring forms as microemulsions, emulsions and liquid crystalline mesophases. The formulations were characterized through the polarization light microscopy, refractive index, relative density, conductivity and behavior rheological. Solubility studies were accomplished showed that the systems were capable to solubilize about 1,5% of caffeine. In vitro release studies using the cell of diffusion model in static system of Franz's type adapted to the dissolution equipment indicated formulations with characteristics of reservoirs systems. The permeability study in vivo used male pig (Landrace x Large White) and they were submitted to the treatment. Formulations with or without caffeine were applied. Skin's fragments and hypoderm of them were removed for histology analysis after the treatment. The formulation with liquid crystal of hexagonal phase characteristics was efficient in increasing skin permeability to the caffeine, thus facilitating its drug action. The application of caffeine this way led to a significant reduction of the hypoderms thickness. The developed system is adjusted for topical use, is skin penetration enhancers and it guarantees the effectiveness of the caffeine in the treatment of the cellulite. / Mestre

Graduation date: 1992

Transdermal drug delivery system has been limited to small and lipophilic drugs because skin has the intrinsic function to protect the body preventing entry of the external species into the body. In this thesis, two physical methods were studied to overcome the skin barrier in the controlled breakage of the skin barrier and to deliver macromolecules-based drugs through the skin; (1) polysaccharide dissolving microneedles and (2) micro thermal skin ablation. Polysaccharide dissolving microneedles system was designed to break the skin barrier in a minimized size with the mechanically poor material, to release them into skin with the dissolution of microneedles, and to deliver human growth hormone into the living hairless rats. Micro thermal skin ablation was designed to fabricate the device generating the energy impact with the basis of arc discharge, to transfer the energy impact on the skin, to remove stratum corneum selectively with three-dimensionally controlled manner, and to deliver hydrophilic macromolecules through skin.

Made available in DSpace on 2014-06-11T19:24:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-08-07Bitstream added on 2014-06-13T20:31:11Z : No. of bitstreams: 1 longo_dp_me_arafcf.pdf: 1190234 bytes, checksum: b0c008283bedbe34e959757962ddfb37 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A mistura de óleo, água e tensoativo é capaz de formar estruturas e sistemas variados, dependendo das características e da proporção dos componentes utilizados. Sistemas microestruturados, como cristais líquidos e microemulsões, são utilizados para encapsular fármacos e substâncias ativas em produtos farmacêuticos e cosméticos. O objetivo desse trabalho foi desenvolver sistemas microestruturados para a incorporação da cafeína com finalidade de uso tópico para otimizar o tratamento da hidrolipodistrofia ginóide. A mistura direta de PPG-5-Ceteth-20 (tensoativo), adipato de dibutila (fase oleosa) e água em diferentes proporções possibilitou a obtenção de formulações com formas de estruturação variadas, como microemulsão, emulsão e mesofases líquido-cristalinas. As formulações obtidas foram caracterizadas por meio de microscopia de luz polarizada, determinação de índice de refração, densidade relativa e condutividade e comportamento reológico. Estudos de solubilidade mostraram que os sistemas foram capazes de solubilizar cerca de 1,5% de cafeína. Estudos de liberação in vitro, que utilizaram modelo de célula de difusão em sistema estático do tipo Franz adaptada ao equipamento de dissolução indicaram que as formulações apresentaram características de sistemas reservatórios de liberação prolongada. Para o estudo de permeação in vivo foram utilizados suínos machos, Landrace x Large White, submetidos ao tratamento com formulação acrescida ou não de cafeína. Fragmentos de pele e hipoderme foram retirados para a análise histológica. A formulação com características de cristal líquido de fase hexagonal foi eficaz em aumentar a permeação cutânea à cafeína, facilitando assim sua ação. A cafeína aplicada desta forma fez com que houvesse uma redução significativa da espessura da hipoderme. O sistema atua como promotor de permeação e garante a eficácia da cafeína no tratamento da celulite. / Oil, water and surfactant mixture may form a variety of structures and phases accordingly to the characteristics and the ratio of the used components. Microcompartmented systems as liquid crystals and microemulsions are used to encapsulated drugs and active substances in pharmaceutical and cosmetic products. The objective of this research was the development of microcompartmented systems for incorporation of caffeine with the purpose of topical use on treatment of the gynoid lipodystrophy. The direct mixture of PPG-5-Ceteth-20 (surfactant), dybutyl adipate (oil phase) and water in differents proportions made possible to obtain formulations with different structuring forms as microemulsions, emulsions and liquid crystalline mesophases. The formulations were characterized through the polarization light microscopy, refractive index, relative density, conductivity and behavior rheological. Solubility studies were accomplished showed that the systems were capable to solubilize about 1,5% of caffeine. In vitro release studies using the cell of diffusion model in static system of Franz's type adapted to the dissolution equipment indicated formulations with characteristics of reservoirs systems. The permeability study in vivo used male pig (Landrace x Large White) and they were submitted to the treatment. Formulations with or without caffeine were applied. Skin's fragments and hypoderm of them were removed for histology analysis after the treatment. The formulation with liquid crystal of hexagonal phase characteristics was efficient in increasing skin permeability to the caffeine, thus facilitating its drug action. The application of caffeine this way led to a significant reduction of the hypoderms thickness. The developed system is adjusted for topical use, is skin penetration enhancers and it guarantees the effectiveness of the caffeine in the treatment of the cellulite.

Yes / Experimental values of permeability coefficients, as log Kp, of chemical compounds across human skin were collected by carefully screening the literature, and adjusted to 37 °C for the effect of temperature. The values of log Kp for partially ionized acids and bases were separated into those for their neutral and ionic species, forming a total data set of 247 compounds and species (including 35 ionic species). The obtained log Kp values have been regressed against Abraham solute descriptors to yield a correlation equation with R2 = 0.866 and SD = 0.432 log units. The equation can provide valid predictions for log Kp of neutral molecules, ions and ionic species, with predictive R2 = 0.858 and predictive SD = 0.445 log units calculated by the leave-one-out statistics. The predicted log Kp values for Na+ and Et4N+ are in good agreement with the observed values. We calculated the values of log Kp of ketoprofen as a function of the pH of the donor solution, and found that log Kp markedly varies only when ketoprofen is largely ionized. This explains why models that neglect ionization of permeants still yield reasonable statistical results. The effect of skin thickness on log Kp was investigated by inclusion of two indicator variables, one for intermediate thickness skin and one for full thickness skin, into the above equation. The newly obtained equations were found to be statistically very close to the above equation. Therefore, the thickness of human skin used makes little difference to the experimental values of log Kp.

Submitted by Erika Demachki (erikademachki@gmail.com) on 2014-09-05T20:11:20Z No. of bitstreams: 2 Alves, Vinicius de Medeiros - 2014.pdf: 3082084 bytes, checksum: da4838d5fe24841429f43de84204d98a (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2014-09-05T20:11:20Z (GMT). No. of bitstreams: 2 Alves, Vinicius de Medeiros - 2014.pdf: 3082084 bytes, checksum: da4838d5fe24841429f43de84204d98a (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2014-03-17 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Repetitive exposure to a chemical agent can induce an immune reaction in inherently susceptible individuals that leads to skin sensitization. Although many chemicals have been reported as skin sensitizers, there have been very few reports analyzing the relationships between their molecular structure and the sensitization potential including the connection to skin permeability, which is widely considered to be mechanistically implicated in sensitization. In this study, we have compiled, curated, and integrated the largest publicly available datasets related to chemically-induced skin sensitization and skin permeability. Unexpectedly, no correlation between sensitization and permeability has been found. Predictive QSAR models have been developed and validated for both skin sensitization and skin permeability using a standardized workflow fully compliant with the OECD guidelines. The classification accuracies of QSAR models discriminating sensitizers from non-sensitizers were 0.68-0.88 when evaluated on several external validation sets. When compared to the predictions generated by the OECD QSAR Toolbox skin sensitization module, our models had significantly higher prediction accuracy for the same sets of external compounds as evaluated by Positive Predicted Rate and Negative Predicted Rate as well as Correct Classification Rate. We have also developed QSAR models of skin permeability measured quantitatively. Cross-species correlation between human and rodent permeability data was found to be low (r²=0.44); thus, skin permeability models were developed using human data only and their external accuracy was q²ext = 0.87 (for 62% of external compounds found within the model applicability domain). Skin sensitization models have been employed to identify putative chemical hazards in the Scorecard database of possible skin or sense organ toxicants that should be regarded as primary candidates for the experimental validation. / A exposição repetida a agentes químicos pode induzir a sensibilização da pele em indivíduos inerentemente suscetíveis e desencadear uma resposta imunológica exacerbada. Apesar de muitos compostos químicos estarem implicados na sensibilização da pele, existem poucos estudos analisando as relações entre a estrutura molecular e o potencial sensibilizador desses compostos, incluindo a conexão com a permeabilidade pela pele, a qual é referida como sendo primordial para o processo de sensibilização. Neste estudo foram compilados, integrados e preparados os maiores conjuntos de dados disponíveis publicamente relacionados tanto com a sensibilização da pele quanto à permeabilidade. Inesperadamente, não se encontrou correlação entre essas duas propriedades. Modelos de QSAR robustos e preditivos foram gerados e validados para ambas as propriedades usando um fluxo de trabalho totalmente complacente com as recomendações da OECD. As taxas de acerto dos modelos discriminaram estruturas sensibilizadoras de não sensibilizadoras com uma taxa de 0,68-0,88 de sucesso, quando avaliadas em vários conjuntos de validação externa. Quando comparados com o módulo de sensibilização da pele implementado na ferramenta QSAR Toolbox da OECD, os modelos tiveram baixa cobertura do espaço químico, mas precisão preditiva mais elevada para os mesmos conjuntos de compostos externos avaliados pelo valor de preditividade positiva e valor de preditividade negativa assim como pela acurácia balanceada. O coeficiente de correlação cruzada entre os dados de permeabilidade da pele humana e de roedores apresentou-se baixo (r²=0,44); assim, apenas o conjunto de dados de pele humana foi considerado para geração de modelos de permeabilidade, que apresentaram precisão externa de q²ext = 0,87 (para 62% dos compostos dentro do domínio de aplicabilidade). Modelos de sensibilização da pele foram empregados para identificação de toxicantes putativos no banco de dados de possíveis agentes toxicantes da Scorecard que podem ser considerados como candidatos para validação experimental.

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