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Investigating electrospinning to prepare nanofibers suitable for neurological disorders
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O presente estudo tem como objetivo investigar o electrospinning como sistema de veiculação de fármacos no tratamento da epilepsia. As fibras fabricadas por electrospinning serão compostas por um fármaco, a carbamazepina (CBZ), e um polímero, o poli(ácido lático-co-ácido glicólico) (PLGA). Os fenómenos térmicos observados por varredura diferencial de calorimetria (DSC) permitiram a interpretação do comportamento do fármaco e do polímero, em diferentes misturas. Como previsto pelas análises molecular e cristalográfica, as duas moléculas não têm tendência para interagir em mistura, e a carbamazepina tende a permanecer sob forma cristalina. Os resultados de DSC poderão significar uma maior estabilidade a longo prazo devido ao seu conteúdo cristalino, hipótese que deverá ser testada. As várias fibras e partículas foram analisadas por microscopia SEM e os parâmetros foram ajustados de forma a obter fibras uniformes de PLGA. Concluiu-se que não só o peso molecular de PLGA, como também a escolha de solvente influencia a formação de nanofibras em virtude de nanopartículas. As fibras de PLGA foram fabricadas com sucesso e os parâmetros ideais para fibras uniformes foram estabelecidos. Estudos morfológicos demonstraram que a capacidade de electrospinning do PLGA aumentou com o aumento do seu peso molecular e que a escolha do solvente influenciou a formação das fibras devido aos seus efeitos nas propriedades reológicas. A análise por DSC das fibras de PLGA demonstrou ser semelhante à análise inicial de PLGA. No entanto, tal não garante um comportamento semelhante entre as misturas de CBZ e PLGA, e as fibras de PLGA com CBZ, pelo que devem continuar a investigar-se o comportamento das fibras com CBZ. O presente estudo demonstra um potencial para o fabrico de fibras de CBZ-PLGA, mas o seu comportamento exato necessita de mais investigação.
The aim of this work was to investigate electrospinning for fabrication of anti-epileptic drug fibers intended for surgical implantation in selected epilepsy patients. Electrospun fibers can potentially be a good alternative to current therapies available, allowing fabrication of coaxial fibers that join chemical and genetic-based therapeutics. Carbamazepine (CBZ) was the selected drug because of its vast therapeutic usage and high efficacy. Thermal analysis with differential scanning calorimetry (DSC) showed that CBZ and PLGA (polylactic-co-glycolic acid), the selected polymer, did not interact and, instead, carbamazepine remained crystalline. This was confirmed by crystal structure data analysis of different carbamazepine forms. However, this data hint that the formulation could be more stable long-term, due to its crystalline content. PLGA fibers were successfully fabricated and ideal parameters for uniform fibers under SEM were established. Morphology studies showed that PLGA electrospinnability increased as its grade also increased, and that the choice of solvent influenced the formation of the fibers due to its effects on rheological properties. The final electrospun PLGA-only fibers DSC analysis showed similar thermal behavior to plain PLGA’s, however, this does not guarantee same behavior from CBZ-PLGA mixtures and CBZ-loaded fibers. The present study demonstrated the potential of CBZ-PLGA fibers, but the exact behavior of the electrospun fibers requires further research.
The aim of this work was to investigate electrospinning for fabrication of anti-epileptic drug fibers intended for surgical implantation in selected epilepsy patients. Electrospun fibers can potentially be a good alternative to current therapies available, allowing fabrication of coaxial fibers that join chemical and genetic-based therapeutics. Carbamazepine (CBZ) was the selected drug because of its vast therapeutic usage and high efficacy. Thermal analysis with differential scanning calorimetry (DSC) showed that CBZ and PLGA (polylactic-co-glycolic acid), the selected polymer, did not interact and, instead, carbamazepine remained crystalline. This was confirmed by crystal structure data analysis of different carbamazepine forms. However, this data hint that the formulation could be more stable long-term, due to its crystalline content. PLGA fibers were successfully fabricated and ideal parameters for uniform fibers under SEM were established. Morphology studies showed that PLGA electrospinnability increased as its grade also increased, and that the choice of solvent influenced the formation of the fibers due to its effects on rheological properties. The final electrospun PLGA-only fibers DSC analysis showed similar thermal behavior to plain PLGA’s, however, this does not guarantee same behavior from CBZ-PLGA mixtures and CBZ-loaded fibers. The present study demonstrated the potential of CBZ-PLGA fibers, but the exact behavior of the electrospun fibers requires further research.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2020, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
Epilepsia Electrospinning Nanofibras Carbamazepina PLGA Mestrado integrado - 2020