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Influence of sucrose as a porogen in the prolonged drug release of PLGA films
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Os polímeros biodegradáveis são atualmente um material com grande potencial para a produção de fármacos com libertação prolongada, devido à sua biocompatibilidade e biodegradabilidade. De facto, o PLGA tem sido amplamente utilizado nas últimas décadas para fabricar diferentes tipos de formulações, incluindo implantes à base de filmes. Existem vários parâmetros que podem ser alterados para modificar as suas propriedades de libertação. Dentre eles, a porosidade de uma matriz pode ter um grande impacto nas formulações, daí a importância de estudar a adição de agentes formadores de poros como os porogens.
Neste estudo, foram preparados filmes de PLGA que utilizaram a sacarose como porogen para avaliar o seu potencial na preparação de formulações de libertação prolongada de fármacos. Além disso, foi também possível explorar o mecanismo de libertação e degradação destes filmes através da utilização de diferentes tamanhos (granel, micronizada e nanosizada versus controlo) e concentrações (5,10,30 e 60%) de sacarose. Os filmes foram caracterizados pelos seguintes métodos: libertação de fármaco in vitro (%), variação do pH, absorção de água (%) e alteração da morfologia.
A adição da sacarose permitiu observar que o efeito de rápida libertação nas primeiras 24 horas foi evitado, à exceção da formulação com 60% de sacarose nanosizada. Em comparação com o controlo, a adição de sacarose mostrou uma libertação mais estável e prolongada no tempo, tornando a sua estrutura mais flexível à libertação do fármaco. Contudo, quando o número de partículas foi demasiado elevado (30 e 60% de sacarose nanosizada), observou-se a destruição da matriz. Em relação à granulometria foi possível observar que tamanhos menores de partículas, por exemplo, 5% da sacarose micronizada ou nanosizada, produziu o mesmo resultado que 10 ou 30% de sacarose a granel.
Em conclusão, perante os resultados obtidos, foi possível confirmar que a sacarose usada como porogen, em diferentes tamanhos e concentrações permite a personalização de sistemas de libertação prolongada de fármacos que utilizam o PLGA na sua matriz.
Biodegradable polymers are currently a material with great potential for the fabrication of drugs with a prolonged release, due to its biocompatibility and biodegradability. In fact, PLGA has been widely used in the last decades to fabricate different types of formulations, including film implants, knowing that several parameters can be changed to alter its release properties. The porosity of a matrix is one of them and can greatly impact the formulations, therefore the importance of studying the addition of pore-forming agents such as porogens. In this experiment, PLGA films that use sucrose as a porogen were prepared, to assess its potential in the preparation of prolonged drug delivery formulations. Through that, it was also possible to explore the drug release and degradation mechanism of these films. To achieve this, different sizes (bulk, micronized and nanosized versus control) and concentrations (5,10,30 and 60%) of sucrose were added and the films were characterized with the following methods: in vitro drug release (%), pH variation, water uptake (%) and morphology change. It was observed that by adding sucrose, the burst effect in the first 24 hours was avoided, except for the 60% nanosized sucrose. Compared with the control, the addition of sucrose displayed a more stable and prolonged release in time, making its structure more flexible to the release of the drug. However, when the number of particles was too high (30 and 60% nanosized sucrose), the destruction of the matrix was seen. Also, when considering a smaller granulometry, 5% of either micronized or nanosized sucrose reached the same results as either 10 or 30% bulk sucrose. In conclusion, the use of sucrose as a porogen in different sizes and concentrations can be used as two advantageous tools for the customization of prolonged drug release delivery systems that use PLGA in its matrix.
Biodegradable polymers are currently a material with great potential for the fabrication of drugs with a prolonged release, due to its biocompatibility and biodegradability. In fact, PLGA has been widely used in the last decades to fabricate different types of formulations, including film implants, knowing that several parameters can be changed to alter its release properties. The porosity of a matrix is one of them and can greatly impact the formulations, therefore the importance of studying the addition of pore-forming agents such as porogens. In this experiment, PLGA films that use sucrose as a porogen were prepared, to assess its potential in the preparation of prolonged drug delivery formulations. Through that, it was also possible to explore the drug release and degradation mechanism of these films. To achieve this, different sizes (bulk, micronized and nanosized versus control) and concentrations (5,10,30 and 60%) of sucrose were added and the films were characterized with the following methods: in vitro drug release (%), pH variation, water uptake (%) and morphology change. It was observed that by adding sucrose, the burst effect in the first 24 hours was avoided, except for the 60% nanosized sucrose. Compared with the control, the addition of sucrose displayed a more stable and prolonged release in time, making its structure more flexible to the release of the drug. However, when the number of particles was too high (30 and 60% nanosized sucrose), the destruction of the matrix was seen. Also, when considering a smaller granulometry, 5% of either micronized or nanosized sucrose reached the same results as either 10 or 30% bulk sucrose. In conclusion, the use of sucrose as a porogen in different sizes and concentrations can be used as two advantageous tools for the customization of prolonged drug release delivery systems that use PLGA in its matrix.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2022, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
Films Prolonged drug release PLGA Porogen Sucrose Mestrado integrado - 2022