Publicação
Preparation and evaluation of an insulin delivery system sensitive to hyperglycaemia
| Resumo: | Diabetes mellitus (DM) represents a world health problem with a current estimated prevalence of 415 million people, characterized by an increased glucose blood concentration. DM type 1 therapy is based on the subcutaneous administration of insulin in accordance to glucose levels, which is associated with patient´s poor compliance. Following this, the aim of this project is to produce an insulin delivery system sensitive to hyperglycaemia, avoiding the need of glycaemia monitoring while promoting a better glucose homeostasis control. In this work, a glucose sensitive insulin delivery system started to be developed based on poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing insulin and catalase and decorated with glucose oxidase (GOx). The principle for insulin release is based on the conversion of glucose into H2O2 whenever glycaemia levels are high; afterwards the breakdown of H2O2 into H2O and O2 by catalase leads to an increased pressure inside the nanoparticles, causing them to break and to release insulin. An initial catalase encapsulation study was conducted. Immobilized catalase was not only active but it also showed increased stability in comparison with free catalase. A release profile could be observed in response to the presence of H2O2. Furthermore, GOx immobilization on PLGA surface was also accomplished and a significant enzymatic activity and stability were achieved. Afterwards, insulin and catalase were co-encapsulated within PLGA nanoparticles and the insulin release pattern was evaluated. However, and in contrast with initial results observed for encapsulated catalase, insulin release was not triggered by the presence of H2O2. The optimized immobilization conditions for catalase are not suitable for insulin delivery probably due to the PLGA surface porosity and insulin smaller size in comparison with catalase. Future work may include the encapsulation of insulin linked to polyethylene glycol (PEG), in order to obtain a larger molecule and by this way avoiding its release through PLGA pores and improving the release of insulin. |
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| Autores principais: | Silva, Rita Leones Alves Reis da |
| Assunto: | Diabetes mellitus Nanoparticles PLGA Insulin Glucose sensitive delivery system Teses de mestrado - 2016 |
| Ano: | 2016 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Diabetes mellitus (DM) represents a world health problem with a current estimated prevalence of 415 million people, characterized by an increased glucose blood concentration. DM type 1 therapy is based on the subcutaneous administration of insulin in accordance to glucose levels, which is associated with patient´s poor compliance. Following this, the aim of this project is to produce an insulin delivery system sensitive to hyperglycaemia, avoiding the need of glycaemia monitoring while promoting a better glucose homeostasis control. In this work, a glucose sensitive insulin delivery system started to be developed based on poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing insulin and catalase and decorated with glucose oxidase (GOx). The principle for insulin release is based on the conversion of glucose into H2O2 whenever glycaemia levels are high; afterwards the breakdown of H2O2 into H2O and O2 by catalase leads to an increased pressure inside the nanoparticles, causing them to break and to release insulin. An initial catalase encapsulation study was conducted. Immobilized catalase was not only active but it also showed increased stability in comparison with free catalase. A release profile could be observed in response to the presence of H2O2. Furthermore, GOx immobilization on PLGA surface was also accomplished and a significant enzymatic activity and stability were achieved. Afterwards, insulin and catalase were co-encapsulated within PLGA nanoparticles and the insulin release pattern was evaluated. However, and in contrast with initial results observed for encapsulated catalase, insulin release was not triggered by the presence of H2O2. The optimized immobilization conditions for catalase are not suitable for insulin delivery probably due to the PLGA surface porosity and insulin smaller size in comparison with catalase. Future work may include the encapsulation of insulin linked to polyethylene glycol (PEG), in order to obtain a larger molecule and by this way avoiding its release through PLGA pores and improving the release of insulin. |
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