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Abstract(s)
desenvolvimento de Sistemas de Entrega de Fármacos utilizando materiais poliméricos
biocompatíveis, recorrendo à manipulação de fibras de celulose na escala nano e à simulação
computacional 3D constitui um exemplo de investigação multidisciplinar na área de Química
Medicinal. O objetivo principal é o desenvolvimento de sistemas de entrega de fármacos
constituídos por uma matriz polimérica 3D de nanocelulose, com otimização da porosidade,
para aplicações em terapêuticas orais em que a libertação controlada apresenta vantagens
relativamente aos sistemas existentes. Utilizou-se a celulose nanofibrilada, desconstruída a
partir da celulose vegetal, comparando-a com a celulose bacteriana, e com a
carboximetilcelulose. Foi possível obter sistemas de entrega de fármacos com cinéticas de
libertação diferenciadas e caracterizar as matrizes produzidas utilizando imagens SEM. A
caracterização das estruturas incluiu a quantificação das dimensões das fibras e dos poros,
recorrendo a programas de análise de imagem. Verificou-se que os sistemas produzidos a
partir de celulose nanofibrilada apresentavam distribuições de tamanhos de poro com maior
variabilidade, o que se traduziu numa cinética de libertação irregular. Posteriormente
efetuou-se a simulação computacional da matriz polimérica e verificou-se que seria possível
obter com os mesmos elementos fibrosos uma matriz com uma distribuição de poros mais
regular. Produziram-se essas estruturas partir da celulose nanofibrilada, controlando as
condições de dispersão das cadeias poliméricas e formação da estrutura 3D do gel, por
manipulação das variáveis de processo da filtração. Utilizou-se a reticulação de um polímero
auxiliar, o alginato, de forma a fixar e manter a estrutura pretendida. A cinética de
libertação do sistema de entrega de fármacos contendo a matriz otimizada permitiu concluir
que a obtenção de poros mais regulares se traduziu numa libertação controlada mais uniforme
e numa melhoria significativa do sistema. Finalmente, produziram-se sistema inovadores
combinando a matriz 3D de celulose nanofibrilada com carboximetilcelulose, uma vez que se
provou que a sua presença permite aumentar a afinidade com a água. Conclui-se que foi
possível evitar a libertação do Diclofenac no pH acídico do estomago e que a simulação
computacional 3D é uma ferramenta útil para projetar sistemas de libertação controlada para
diferentes aplicações terapêuticas.
The development of Drug Delivery Systems using biocompatible polymeric materials, with manipulation of cellulose fibers at the nano scale and 3D computer simulation, is an example of multidisciplinary research in the field of Medicinal Chemistry. The main purpose is the development of drug delivery systems consisting of a 3D polymer matrix of nanocellulose, with porosity optimization, for applications in oral therapeutics in which controlled release presents advantages over existing systems. The nanofibrillated cellulose, deconstructed from vegetable cellulose, was compared to bacterial cellulose and carboxymethylcellulose. It was possible to obtain drug delivery systems with differentiated release kinetics and to characterize the matrices produced using SEM images. The characterization of the structures included the quantification of the dimensions of the fibers and the pores, using image analysis software’s. Systems produced from nanofibrillated cellulose were found to have pore size distributions with greater variability, which resulted in irregular release kinetics. By using the computational simulation of the polymer matrix, it was verified that it would be possible to obtain a matrix with a more regular pore distribution with the same fibrous elements. These structures were produced from the nanofibrillated cellulose, controlling the conditions of dispersion of the polymer chains and formation of the 3D structure of the gel, by manipulation of the process variables of the filtration. Crosslinking of an auxiliary polymer, the alginate, was used to fix and maintain the desired structure. The release kinetics of the drug delivery system containing the optimized nanocellulose matrix have proved that more regular pores resulted in a more uniform release kinetics and a significant improvement of the system. Finally, innovative systems were produced by combining the 3D matrix of nanofibrillated cellulose with carboxymethylcellulose, since it has been proved that its presence allows the increase of the affinity with water. It has been concluded that it was possible to avoid the release of Diclofenac in the acidic pH of the stomach and that the 3D computational simulation is a useful tool to design controlled release systems for different therapeutic applications.
The development of Drug Delivery Systems using biocompatible polymeric materials, with manipulation of cellulose fibers at the nano scale and 3D computer simulation, is an example of multidisciplinary research in the field of Medicinal Chemistry. The main purpose is the development of drug delivery systems consisting of a 3D polymer matrix of nanocellulose, with porosity optimization, for applications in oral therapeutics in which controlled release presents advantages over existing systems. The nanofibrillated cellulose, deconstructed from vegetable cellulose, was compared to bacterial cellulose and carboxymethylcellulose. It was possible to obtain drug delivery systems with differentiated release kinetics and to characterize the matrices produced using SEM images. The characterization of the structures included the quantification of the dimensions of the fibers and the pores, using image analysis software’s. Systems produced from nanofibrillated cellulose were found to have pore size distributions with greater variability, which resulted in irregular release kinetics. By using the computational simulation of the polymer matrix, it was verified that it would be possible to obtain a matrix with a more regular pore distribution with the same fibrous elements. These structures were produced from the nanofibrillated cellulose, controlling the conditions of dispersion of the polymer chains and formation of the 3D structure of the gel, by manipulation of the process variables of the filtration. Crosslinking of an auxiliary polymer, the alginate, was used to fix and maintain the desired structure. The release kinetics of the drug delivery system containing the optimized nanocellulose matrix have proved that more regular pores resulted in a more uniform release kinetics and a significant improvement of the system. Finally, innovative systems were produced by combining the 3D matrix of nanofibrillated cellulose with carboxymethylcellulose, since it has been proved that its presence allows the increase of the affinity with water. It has been concluded that it was possible to avoid the release of Diclofenac in the acidic pH of the stomach and that the 3D computational simulation is a useful tool to design controlled release systems for different therapeutic applications.
Description
Keywords
Celulose Nanofibrilada Cinética de Libertação Controlada Porosidade Simulação
Computacional 3d Sistemas de Entrega de Fármacos