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Authors
Abstract(s)
O glaucoma é uma doença degenerativa ocular que prejudica o nervo ótico do olho, o
que leva a um aumento da pressão intraocular (IOP) e pode resultar em perda total e
irreversível de visão. O tratamento disponível até há data baseia-se na administração do
fármaco brimonidina através de gotas oculares de forma a diminuir a IOP. Porém, a adesão
dos pacientes ao tratamento de administração de gotas é, em geral, baixa, o que conduz ao
agravamento da doença. O objetivo desta tese foi desenvolver um filme biocompatível que
possa servir de revestimento para um dispositivo intraocular, que permita a libertação da
brimonidina de forma programada, autónoma e in situ. Os filmes foram preparados pela
técnica camada-sobre-camada e são compostos por monocamadas de brimonidina
encapsulada em 2-hidroxipropil-ß-ciclodextrina intercaladas por camadas que atrasam a
libertação do fármaco e que se designam por camadas barreira. Estas últimas são compostas
por um polímero hidrossolúvel (PBAE) e por bicamadas de óxido de grafeno (GO) compostas
por grafeno positivo funcionalizado com grupos amina protonados (GONH3
+) e por grafeno
negativo funcionalizado com grupos carboxílicos desprotonados (COO-). Foram preparados
três tipos de filmes, a diferença entre os dois primeiros filmes foi a alteração da ordem das
camadas de GO de forma a verificar a sua interação com a camada de brimonidina e o terceiro
filme apenas contém um tipo de camada barreira compostas por GO, retirando-se o polímero
hidrossolúvel PBAE, de forma a verificar a sua influencia na cinética de libertação da
brimonidina. O crescimento dos filmes foi monitorizado por espectroscopia de absorção no
ultravioleta e visível (UV-Vis) e microscopia de força atómica (AFM) e a cinética de libertação
do fármaco foi controlada por UV-Vis e por cromatografia líquida de alta eficiência (HPLC). Os
resultados mostraram que os filmes são estáveis e que a libertação do fármaco pode ser
controlada pela presença do polímero hidrossolúvel e do óxido de grafeno. Nomeadamente,
a presença de GO atrasa a libertação de brimonidina por vários dias dependendo do número
de camadas existentes no filme.
Glaucoma is an ocular degenerative disease that damages the eye’s topic nerve, this leading to an intraocular pressure (IOP) increase which can result in a total and irreversible loss of vision. The available treatment at the moment is based on brimonidine administration which allows the decrease of IOP, by administration of ocular drops, in order to decrease IOP. However, adherence of patients to the treatment of droplet administration is generally low, which leads to the worsening of the disease. The aim of this thesis was to develop a biocompatible film that can serve as coating for an intraocular device, allowing the brimonidine release to be programmed, autonomous and in situ. The films were prepared by layer-on-layer technique and were composed of brimonidine monolayers encapsulated in 2-hydroxypropyl- β-cyclodextrin interspersed by layers that delay drug release and are referred to as barrier layers. These layers are composed of a water soluble polymer (PBAE) and graphene oxide (GO) composites composed of graphene positive functionalized with protonated amine groups (GONH3+) and negative graphene functionalized with deprotonated carboxylic groups (COO- ). Three types of films were prepared, the difference between the first two films was the change in the order of the GO layers in order to verify their interaction with the brimonidine layer and the third film only contains a type of barrier layer composed of GO, by removing the water soluble polymer PBAE, in order to verify its influence on the brimonidine release kinetics. The film growth was monitorized by ultraviolet-visible absorption spectroscopy (UV-Vis) and atomic force microscopy (AFM) and the drug release kinetics was followed by UV-Vis absorption spectroscopy and high performance liquid chromatography (HPLC). The results have shown that the obtained films are stable and the drug release can be controlled by the presence of the hydrossoluble polymer and the graphene oxide. Notably, the presence of GO layers delays the brimonidine release for several days depending on the number of layers in the film.
Glaucoma is an ocular degenerative disease that damages the eye’s topic nerve, this leading to an intraocular pressure (IOP) increase which can result in a total and irreversible loss of vision. The available treatment at the moment is based on brimonidine administration which allows the decrease of IOP, by administration of ocular drops, in order to decrease IOP. However, adherence of patients to the treatment of droplet administration is generally low, which leads to the worsening of the disease. The aim of this thesis was to develop a biocompatible film that can serve as coating for an intraocular device, allowing the brimonidine release to be programmed, autonomous and in situ. The films were prepared by layer-on-layer technique and were composed of brimonidine monolayers encapsulated in 2-hydroxypropyl- β-cyclodextrin interspersed by layers that delay drug release and are referred to as barrier layers. These layers are composed of a water soluble polymer (PBAE) and graphene oxide (GO) composites composed of graphene positive functionalized with protonated amine groups (GONH3+) and negative graphene functionalized with deprotonated carboxylic groups (COO- ). Three types of films were prepared, the difference between the first two films was the change in the order of the GO layers in order to verify their interaction with the brimonidine layer and the third film only contains a type of barrier layer composed of GO, by removing the water soluble polymer PBAE, in order to verify its influence on the brimonidine release kinetics. The film growth was monitorized by ultraviolet-visible absorption spectroscopy (UV-Vis) and atomic force microscopy (AFM) and the drug release kinetics was followed by UV-Vis absorption spectroscopy and high performance liquid chromatography (HPLC). The results have shown that the obtained films are stable and the drug release can be controlled by the presence of the hydrossoluble polymer and the graphene oxide. Notably, the presence of GO layers delays the brimonidine release for several days depending on the number of layers in the film.
Description
Trabalho final de mestrado para obtenção do grau de mestre em Engenharia Biomédica
Keywords
Camada-sobre-camada Layer-by-layer Libertação controlada de fármacos Controlled drug delivery Brimonidina Brimonidine 2-hidroxipropil-β-ciclodextrina e óxido de grafeno 2-hydroxypropyl- β-cyclodextrin and graphene oxide Glaucoma
Citation
MORAIS, Helena Isabel Costa - Nanostructured films of graphene for controlled ocular drug delivery. Lisboa: Instituto Superior de Engenharia de Lisboa - Escola Superior de Tecnologia da Saúde de Lisboa, 2017. Dissertação de mestrado.
Publisher
Instituto Superior de Engenharia de Lisboa - Escola Superior de Tecnologia da Saúde de Lisboa