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Abstract(s)
Neste trabalho foram sintetizados hidrogéis inteligentes, sensíveis ao pH e à temperatura, tendo sido também realizados testes de libertação de quatro fármacos diferentes a partir dos materiais preparados.
Com o objetivo de estudar o efeito das condições de síntese sobre as propriedades e desempenho dos hidrogéis, foi feita a sua produção em suspensão inversa (a morfologia das partículas obtidas foi analisada por microscopia eletrónica de varrimento – SEM) e em solução. Foram considerados dois mecanismos diferentes de reação: polimerização radicalar clássica (FRP) e a polimerização por transferência de cadeia reversível por adição-fragmentação (RAFT).
Usando diferentes combinações dos monómeros de partida, foram sintetizados hidrogéis polielectrólitos de diferentes tipos, nomeadamente aniónicos, catiónicos e anfotéricos e também hidrogéis não iónicos. Foi observada a efetiva sensibilidade dos materiais obtidos à variação das condições envolventes, nomeadamente variações no pH de soluções aquosas, temperatura, força iónica ou presença de solvente desidratante. Demonstrou-se assim a possibilidade de fazer transitar os hidrogéis entre estados de inchamento/colapso em consequência da alteração de parâmetros pré-definidos.
As propriedades únicas destes materiais foram exploradas na libertação estimulada de fármacos, nomeadamente de 5-fluoruracilo (usado no tratamento do cancro), ibuprofeno (anti-inflamatório/analgésico), isoniazida (usada no tratamento da tuberculose) e cafeína (atuador do sistema nervoso central). As dinâmicas de libertação dos fármacos foram medidas experimentalmente através de espectroscopia de ultravioleta. Neste contexto, foram consideradas diferentes combinações hidrogel/estímulo/fármaco tendo em vista a procura de condições que possam potenciar os processos de libertação. Fez-se também uma descrição mecanicista simples da dinâmica de libertação dos fármacos, considerando para esse efeito modelos matemáticos alternativos (modelo exponencial e lei de potência).
Esta investigação procura contribuir para o desenvolvimento de ferramentas que possam ser usadas no projeto de condições de síntese, visando a produção de materiais avançados com propriedades por medida e com aplicações em biomedicina.
This work was devoted to the synthesis of smart hydrogels with sensitivity to pH and temperature. Considering four different drugs, these advanced materials were also tested for drug delivery purposes. Aiming the study of the effect of the synthesis conditions on the properties and performance of the hydrogels, these materials were produced using inverse-suspension polymerization (the morphology of the obtained particles was analyzed by Scanning Electronic Microscopy - SEM) and also considering solution polymerization. Two different polymerization mechanisms were also considered: classical free radical polymerization (FRP) and Reversible Addition-Fragmentation chain Transfer (RAFT) polymerization. By using different combinations of the initial monomers, different kinds of polyelectrolyte hydrogels were synthetized, namely anionic, cationic and amphoteric. Non-ionic hydrogels were also produced. It was observed that the materials produced are effectively sensitive to changes in the surrounding conditions, namely changes in pH of aqueous solutions, temperature, ionic strength and the presence of a dehydrating solvent. It was thus showed the ability to trigger the transition of hydrogels between swollen/shrunken states as a result of the change of pre-defined parameters. The unique properties of these materials were explored in the stimulated release of drugs, namely 5-fluorouracil (used in cancer treatment), ibuprofen (anti-inflammatory/analgesic), isonicotinic acid (used in tuberculosis treatment) and caffeine (stimulant of the central nervous system). The dynamics of release of these drugs were experimentally measured using ultraviolet spectroscopy. In the framework of these studies, different combinations between hydrogel/stimuli/drug were considered, aiming the search of conditions enhancing the drug release processes. A simple mechanistic description of the dynamics of drug release was also performed considering two alternative mathematical models (exponential and power laws). This research aims to contribute to the development of tools that can be used in the designs of synthesis conditions useful in the production of advanced materials with tailored properties that find applications in biomedicine.
This work was devoted to the synthesis of smart hydrogels with sensitivity to pH and temperature. Considering four different drugs, these advanced materials were also tested for drug delivery purposes. Aiming the study of the effect of the synthesis conditions on the properties and performance of the hydrogels, these materials were produced using inverse-suspension polymerization (the morphology of the obtained particles was analyzed by Scanning Electronic Microscopy - SEM) and also considering solution polymerization. Two different polymerization mechanisms were also considered: classical free radical polymerization (FRP) and Reversible Addition-Fragmentation chain Transfer (RAFT) polymerization. By using different combinations of the initial monomers, different kinds of polyelectrolyte hydrogels were synthetized, namely anionic, cationic and amphoteric. Non-ionic hydrogels were also produced. It was observed that the materials produced are effectively sensitive to changes in the surrounding conditions, namely changes in pH of aqueous solutions, temperature, ionic strength and the presence of a dehydrating solvent. It was thus showed the ability to trigger the transition of hydrogels between swollen/shrunken states as a result of the change of pre-defined parameters. The unique properties of these materials were explored in the stimulated release of drugs, namely 5-fluorouracil (used in cancer treatment), ibuprofen (anti-inflammatory/analgesic), isonicotinic acid (used in tuberculosis treatment) and caffeine (stimulant of the central nervous system). The dynamics of release of these drugs were experimentally measured using ultraviolet spectroscopy. In the framework of these studies, different combinations between hydrogel/stimuli/drug were considered, aiming the search of conditions enhancing the drug release processes. A simple mechanistic description of the dynamics of drug release was also performed considering two alternative mathematical models (exponential and power laws). This research aims to contribute to the development of tools that can be used in the designs of synthesis conditions useful in the production of advanced materials with tailored properties that find applications in biomedicine.
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Keywords
Hidrogéis Estímulos Libertação Fármacos