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O peróxido de hidrogénio é um composto crítico para os seres vivos. A baixas concentrações, assume funções regulatórias de extrema importância, enquanto a altas concentrações, exibe toxicidade. Graças ao seu papel na biologia dos organismos, é possível desenhar terapias de peróxido de hidrogénio, que se direcionem a alvos moleculares específicos, para aplicações em cicatrização de feridas, diabetes ou obesidade. Por outro lado, usando vapores concentrados em peróxido de hidrogénio, a sua toxicidade pode ser usada para eliminar microrganismos, num processo de descontaminação.
Neste trabalho, compostos sólidos foram funcionalizados para libertar peróxido de hidrogénio, num perfil de libertação adaptado à sua aplicação. Para aplicações médicas, a funcionalização providencia um perfil de libertação lento de uma reduzida concentração de peróxido de hidrogénio. Para fins industriais, os compostos sólidos libertam rapidamente uma alta concentração de peróxido de hidrogénio. Um protocolo de funcionalização com proteína foi desenvolvido e otimizado. O objetivo era capacitar os compostos sólidos de serem direcionados para alvos moleculares específicos, para que o peróxido de hidrogénio pudesse ser libertado na sua vizinhança, resultando em baixa citotoxicidade. Ademais, as condições ideais para cicatrização foram determinadas por ensaios scratch. Finalmente, os compostos sólidos foram testados em termos da sua citotoxicidade, de forma a se selecionarem os melhores deles para continuar os estudos.
Em conclusão, compostos sólidos modificáveis foram desenhados para corresponder a perfis de libertação de peróxido de hidrogénio específicos.
Hydrogen peroxide is a critical compound for living beings. In low concentrations, it assumes important regulatory functions, while in high concentrations, it exhibits toxicity. Due to its role in the organisms’ biology, it is possible to design hydrogen peroxide-based therapies that aim specific targets, including applications in wound healing, diabetes or obesity. On the other side, by using high vapour concentrations of hydrogen peroxide, its toxicity can be put to use to kill microorganisms, in a decontamination process. In this work, solid compounds were functionalized to deliver hydrogen peroxide, in a releasing profile adapted to its application. For medical applications, the functionalization provided a slow releasing profile of a low concentration of hydrogen peroxide. For industrial purposes, the solid compounds released a fast and high amount of hydrogen peroxide. A protocol of functionalization with protein was developed and optimized. The goal was to capacitate the solid compounds to be directed to specific targets, so the hydrogen peroxide could be released in its vicinity, leading to low cytotoxicity. Moreover, the ideal conditions for wound healing were determined by scratch assays. Finally, solid compounds were tested for cytotoxicity, in order to select the best of them to proceed the studies. In conclusion, changeable solid compounds were designed to match a specific hydrogen peroxide release profile.
Hydrogen peroxide is a critical compound for living beings. In low concentrations, it assumes important regulatory functions, while in high concentrations, it exhibits toxicity. Due to its role in the organisms’ biology, it is possible to design hydrogen peroxide-based therapies that aim specific targets, including applications in wound healing, diabetes or obesity. On the other side, by using high vapour concentrations of hydrogen peroxide, its toxicity can be put to use to kill microorganisms, in a decontamination process. In this work, solid compounds were functionalized to deliver hydrogen peroxide, in a releasing profile adapted to its application. For medical applications, the functionalization provided a slow releasing profile of a low concentration of hydrogen peroxide. For industrial purposes, the solid compounds released a fast and high amount of hydrogen peroxide. A protocol of functionalization with protein was developed and optimized. The goal was to capacitate the solid compounds to be directed to specific targets, so the hydrogen peroxide could be released in its vicinity, leading to low cytotoxicity. Moreover, the ideal conditions for wound healing were determined by scratch assays. Finally, solid compounds were tested for cytotoxicity, in order to select the best of them to proceed the studies. In conclusion, changeable solid compounds were designed to match a specific hydrogen peroxide release profile.
Descrição
Tese de mestrado em Bioquímica, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2016
Palavras-chave
Peróxido de hidrogénio Compostos sólidos Cicatrização Diabetes Descontaminação Teses de mestrado - 2016
