Cápsulas supramoleculares derivadas de redes metalo-orgânicas para liberação de fármaco
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Data
2020-09-24
Autores
Abuçafy, Marina Paiva
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Universidade Estadual Paulista (Unesp)
Resumo
As redes metalo-orgânicas são polímeros de coordenação cristalinos e altamente porosos constituídos por interações covalentes entre íons ou clusters metálicos e ligantes orgânicos. Dentre algumas superestruturas que podem ser construídas com base em MOFs, destacam-se as cápsulas, que tem atraído muito interesse dos pesquisadores por ser um material que além da porosidade usualmente encontrada neste tipo de material, podem apresentar cavidades no seu interior. O uso de cápsulas construídas a partir de MOFs como sistemas de liberação de fármaco tem progredido, particularmente para superar as limitações dos carreadores já explorados pela literatura, proporcionando a possibilidade de transportar moléculas grandes ou uma elevada massa da molécula de interesse. Dentro desse contexo, foram desenvolvidas nesse trabalho cápsulas à base das MOFs HKUST, ZIF-8 e MIL-100 por três métodos diferentes: utilização de moldes, emulsão de pickering e spray drying, com o objetivo de formar um sistema de duplo carreamento para o tratamento de câncer. Os materiais foram caracterizados físico-quimicamente e as cápsulas à base da MIL-100 desenvolvidas por spray drying mostraram-se mais promissoras para a aplicação farmacêutica, apresentando diametro médio de 800 nm. As cápsulas exibiram maior eficiência de encapsulação para o fármaco metotrexato (MTX) quando comparada com a sua oclusão em nanopartículas do mesmo material, o que corrobora com as suas propriedades e a presença de cavidades ocas observadas por microscopia eletrônica, além do aumento de tamanho do sistema. Além disso, as cápsulas apresentaram também uma alta capacidade de encapsulação de moléculas grandes, como a enzima colagenase (91,7%). O ensaio de atividade enzimática mostrou que a colagenase permaneceu com sua atividade preservada mesmo após o processo de encapsulação. Quanto aos processos de liberação da matriz porosa, o perfil de liberação do fármaco MTX mostrou que as cápsulas têm maior capacidade para prolongar a liberação do metotrexato, de maneira que após 48 horas, apenas 50% do fármaco foi liberado, enquanto quase 93% do fármaco presente na nanopartículas da MOF MIL-100 já haviam sido liberados, o que também pode ser justificado pela maior área superfícial da nanopartícula. Além disso, a cápsula também controla a liberação da colagenase, permitindo o uso desse sistema como um material capaz de transportar e liberar o fármaco e a enzima em associação. A avaliação da citotoxicidade em células e A-375 revelou alta viabilidade celular das cápsulas de MIL-100 e, que após 24 horas de incubação, as cápsulas contendo MTX e colagenase causaram aumento da citotoxicidade, principalmente na linhagem celular cancerígena, o que confirma a ação antitumoral do sistema composto pelo fármaco e pela proteína.
Metal-Organic Frameworks are highly porous and crystalline coordination polymers made up of covalent interactions between metallic ions or clusters and organic ligands. Among some superstructures that can be developed based on MOFs, the capsules stand out, which has attracted a lot of interest from researchers because it is a material that, in addition to the porosity usually found in this type of material, can have cavities (hollow capsules) inside. The use of capsules based on MOFs as drug delivery systems has progressed, particularly to overcome the limitations of carriers already explored in the literature, providing the possibility of transporting large molecules or a high mass of the molecule of interest. Within this context, capsules based on MOFs HKUST, ZIF-8 and MIL-100 (Fe) were developed in this work by three different methods: using molds, pickering emulsion and spray drying, aiming to form a double loading system for the treatment of cancer. The materials were physically and chemically characterized and the capsules based on MIL-100 (Fe) developed by spray drying proved to be more promising for pharmaceutical application, presenting an average diameter of 800 nm. The capsules exhibited greater encapsulation efficiency for the drug methotrexate (MTX) when compared to its occlusion in nanoparticles of the same material, which corroborates with its properties and the presence of hollow cavities observed by electron microscopy, besides the increase of the system size. In addition, the capsules also showed a high capacity to encapsulate large molecules, such as the collagenase enzyme (91.7%). The enzyme activity test showed that the collagenase remained with its activity preserved even after the process of encapsulation by spray drying. As for the release processes of the porous matrix, the MTX drug release profile showed that the capsules have a greater capacity to prolong the release of methotrexate, so that after 48 hours, only 50% of the drug was released, while almost 93% of the drug was released. drug present in the MOF MIL-100 nanoparticles had already been released, which can also be justified by the larger surface area of the nanoparticle. In addition, the capsule also controls the release of collagenase, allowing the use of this system as a material capable of transporting and releasing the drug and enzyme in combination. The evaluation of cytotoxicity in HaCat and A-375 cells revealed high cell viability of MIL-100 (Fe) capsules and, after 24 hours of incubation, capsules containing MTX and collagenase caused an increase in cytotoxicity, mainly in the cancer cell line, which confirms the antitumor action of the system composed of the drug and the protein.
Metal-Organic Frameworks are highly porous and crystalline coordination polymers made up of covalent interactions between metallic ions or clusters and organic ligands. Among some superstructures that can be developed based on MOFs, the capsules stand out, which has attracted a lot of interest from researchers because it is a material that, in addition to the porosity usually found in this type of material, can have cavities (hollow capsules) inside. The use of capsules based on MOFs as drug delivery systems has progressed, particularly to overcome the limitations of carriers already explored in the literature, providing the possibility of transporting large molecules or a high mass of the molecule of interest. Within this context, capsules based on MOFs HKUST, ZIF-8 and MIL-100 (Fe) were developed in this work by three different methods: using molds, pickering emulsion and spray drying, aiming to form a double loading system for the treatment of cancer. The materials were physically and chemically characterized and the capsules based on MIL-100 (Fe) developed by spray drying proved to be more promising for pharmaceutical application, presenting an average diameter of 800 nm. The capsules exhibited greater encapsulation efficiency for the drug methotrexate (MTX) when compared to its occlusion in nanoparticles of the same material, which corroborates with its properties and the presence of hollow cavities observed by electron microscopy, besides the increase of the system size. In addition, the capsules also showed a high capacity to encapsulate large molecules, such as the collagenase enzyme (91.7%). The enzyme activity test showed that the collagenase remained with its activity preserved even after the process of encapsulation by spray drying. As for the release processes of the porous matrix, the MTX drug release profile showed that the capsules have a greater capacity to prolong the release of methotrexate, so that after 48 hours, only 50% of the drug was released, while almost 93% of the drug was released. drug present in the MOF MIL-100 nanoparticles had already been released, which can also be justified by the larger surface area of the nanoparticle. In addition, the capsule also controls the release of collagenase, allowing the use of this system as a material capable of transporting and releasing the drug and enzyme in combination. The evaluation of cytotoxicity in HaCat and A-375 cells revealed high cell viability of MIL-100 (Fe) capsules and, after 24 hours of incubation, capsules containing MTX and collagenase caused an increase in cytotoxicity, mainly in the cancer cell line, which confirms the antitumor action of the system composed of the drug and the protein.
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Palavras-chave
Cápsulas de MOF, metotrexato,, colagenase, sistemas duplos de liberação, MOF capsules, methotrexate, collagenase, dual release systems