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Advisor(s)
Abstract(s)
O desenvolvimento de sistemas de entrega de fármacos é uma das áreas de Química Medicinal com as aplicações mais promissoras e que beneficia de uma abordagem multidisciplinar incluindo nanotecnologia, modelação computacional e análise de imagem. O planeamento experimental permitiu obter sistemas de entrega inovadores e com cinéticas de libertação diferentes, a partir da combinação de diferentes unidades estruturais poliméricas. Produziram-se e caracterizaram-se estruturas obtidas a partir da celulose, com fibrilações na escala micro (CMF) e nano (CNF), e estruturas álcool polivinílico (PVA) obtidas por “electrospinning”. Desenvolveu-se uma metodologia de tratamento de imagem que se aplicou às imagens obtidas por microscopia eletrónica de varrimento (MEV), permitindo identificar as características chave e os critérios de análise de imagem para obtenção das dimensões das fibras e dos poros das estruturas, nas diferentes escalas. As propriedades morfológicas na escala micro, em suspensão fibrosa, foram também determinadas utilizando um equipamento designado por “Morfi”, sendo que o diâmetro médio das fibras de CMF em suspensão foi de 20 µm. Além da caracterização estrutural, incluindo a espessura e a porosidade das estruturas, determinou-se a sua hidrofobicidade das estruturas de CMF através do ângulo de contacto, com valores que variam entre 47º e 56º. Os resultados provenientes dos métodos de análise de imagem 2D para as dimensões das fibras utilizaram-se como dados de entrada para formar a estrutura 3D no simulador computacional. A validação foi feita comparando os valores de porosidade das estruturas obtidas por simulação computacional com as estruturas reais, utilizando o mesmo procedimento para o seu tratamento e análise. O estudo da cinética da libertação do fármaco Diclofenac provou que sistemas de entrega de fármacos com porosidades diferentes têm cinéticas de libertação diferentes. Conclui-se que se pode utilizar a metodologia de análise de imagem apresentada neste trabalho, juntamente com a simulação computacional, para otimizar a porosidade de nanomateriais porosos, de forma a otimizar o transporte de moléculas terapêuticas.
The development of drug delivery systems is one of the medicinal chemistry areas with the most promising applications and benefits of a multidisciplinary approach including nanotechnology, computational modelling and image analysis. The work plan yielded innovative drug delivery systems with different release kinetics, based on the combination of different polymeric structural units. Structures obtained from cellulose, with micro (MFC) and nano fibrillation (CNF) have been produced and characterized, and structures made from polyvinyl alcohol (PVA) have been obtained by electrospinning. A method for image processing that is applied to images obtained by electron microscopy scanning (SEM) was developed, allowing the identification of key features and image analysis criteria, in order to obtain the fiber and pore dimensions in different scales. The micro-scale morphological properties, in fiber suspension, were also determined using a device designated as "Morfi", wherein the average fiber diameter of the MFC in suspension was 20 µm. Besides structural characterization, including the thickness and porosity of the structures, it was determined the hydrophobicity of MFC structures by contact angle, with values ranging between 47º and 56º. The results of fiber dimensions from the 2D image analysis techniques were used as input data to form the 3D structure of the computer simulation. Validation was done by comparing the porosity values of the structures obtained by computer simulation with real structures, using the same procedure for treatment and analysis. The release kinetic study of Diclofenac proved that drug delivery systems with different porosities have different kinetics of release. In conclusion, the image analysis method presented here can be used along with the simulation to optimize the porosity of porous nanomaterials, in order to optimize the delivery of therapeutic molecules.
The development of drug delivery systems is one of the medicinal chemistry areas with the most promising applications and benefits of a multidisciplinary approach including nanotechnology, computational modelling and image analysis. The work plan yielded innovative drug delivery systems with different release kinetics, based on the combination of different polymeric structural units. Structures obtained from cellulose, with micro (MFC) and nano fibrillation (CNF) have been produced and characterized, and structures made from polyvinyl alcohol (PVA) have been obtained by electrospinning. A method for image processing that is applied to images obtained by electron microscopy scanning (SEM) was developed, allowing the identification of key features and image analysis criteria, in order to obtain the fiber and pore dimensions in different scales. The micro-scale morphological properties, in fiber suspension, were also determined using a device designated as "Morfi", wherein the average fiber diameter of the MFC in suspension was 20 µm. Besides structural characterization, including the thickness and porosity of the structures, it was determined the hydrophobicity of MFC structures by contact angle, with values ranging between 47º and 56º. The results of fiber dimensions from the 2D image analysis techniques were used as input data to form the 3D structure of the computer simulation. Validation was done by comparing the porosity values of the structures obtained by computer simulation with real structures, using the same procedure for treatment and analysis. The release kinetic study of Diclofenac proved that drug delivery systems with different porosities have different kinetics of release. In conclusion, the image analysis method presented here can be used along with the simulation to optimize the porosity of porous nanomaterials, in order to optimize the delivery of therapeutic molecules.
Description
Keywords
Celulose Microfibrilada Celulose Nanofibrilada Estruturas Poliméricas Porosas 3d Nanomateriais Simulação Computacional Sistemas de Entrega de Fármacos