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Nanopartículas como sistemas transportadores de proteínas
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Abstract(s)
Desde a introdução da insulina no mercado que as terapias à base de proteínas têm sido alvo de estudo e desenvolvimento em áreas e doenças, como a oncologia, doenças cardiovasculares, doenças metabólicas e infeciosas. Estes agentes terapêuticos são biomacromoléculas de grandes dimensões, com parâmetros de estabilidade estreitos e com conformações estruturais que lhes conferem especificidade no seu modo de acção e também problemas na sua administração. Fenómenos como a baixa biodisponibilidade devido à degradação enzimática ou imunogenicidade ou à baixa internalização nas células são as grandes razões para a dificuldade da aplicação desta classe terapêutica. A Aplicação de sistemas de veiculação de fármacos (Drug Delivery Systems, DDS) com recurso à nanotecnologia, tem sido uma estratégia para a administração de proteínas. Estes sistemas são transportadores biocompatíveis e biodegradáveis existentes à escala nanométrica que transportam o fármaco, ao local de ação de forma seletiva através da aplicação de ligandos específicos e protegem o mesmo durante o transporte, de modo a evitar a degradação ou desnaturação da proteína, levando a uma libertação prolongada no local de ação.
Existem vários tipos de nanopartículas com aplicações e especificidades diferentes que dependem da sua composição e das propriedades como o tamanho, formato, hidrofobicidade e potencial zeta. Estas propriedades são controladas durante a produção do nanotransportador de forma a que a nanopartícula seja a mais adequada ao fármaco. Enquanto na sua constituição estão presentes materiais à escala nanométrica, como os lípidos, os polímeros ou materiais inorgânicos como, por exemplo, a sílica. A aplicação desta tecnologia na administração de proteínas e péptidos terapêuticos tem alcançado resultados promissores, tais como o aumento da biodisponibilidade e da semivida das proteínas em diversos estudos. Atualmente já foram introduzidos no mercado vários medicamentos à base de proteínas recombinadas na qual é aplicada a nanotecnologia nos seus sistemas de veiculação de fármacos.
Since the introduction of insulin on the market, protein-based therapies have been the target of study and development, to be used in diseases, such as cancer and cardiovascular, metabolic and infectious diseases. These therapeutic agents are large biomacromolecules with narrow stability parameters and structural conformations that confers specificity to the binding site and difficulties in its administration. Phenomena such as low bioavailability due to enzymatic degradation or immunogenicity or low level of cell internalization are the main reasons for the difficulties in applying this therapeutic class. The use of drug delivery systems (DDS) through the application of nanotechnology, the use of drug delivery systems (DDS) has been a strategy for the administration of proteins. These systems are biocompatible and biodegradable transporters that exist in the scale of nanometers and are used in the selectived delivery of the drug to the action site by applying targeting ligands to their surface. These systems also protect the drug from possible degradation or denaturation during the transport, thus contributing to a prolonged release at the site of action. There are several types of nanoparticles with different applications and specificities which are dependent on their nanomaterial and properties such as size, shape, hidrophobicity and zeta potential. These properties are controlled during the production of the nanotransporter, with the aim to make the nanoparticle suitable for the intended drug. While in its constitution there are materials, such as lipids, polymers, or inorganic materials such as silica. The application of this technology for the administration of therapeutic proteins and peptides has achieved promising results, such as increased bioavailability and half-life of the drug in circulation in several studies. In the modern days, several drugs based on recombinant proteins have been introduced on the market, in which nanotechnology in applied in their drug delivery systems.
Since the introduction of insulin on the market, protein-based therapies have been the target of study and development, to be used in diseases, such as cancer and cardiovascular, metabolic and infectious diseases. These therapeutic agents are large biomacromolecules with narrow stability parameters and structural conformations that confers specificity to the binding site and difficulties in its administration. Phenomena such as low bioavailability due to enzymatic degradation or immunogenicity or low level of cell internalization are the main reasons for the difficulties in applying this therapeutic class. The use of drug delivery systems (DDS) through the application of nanotechnology, the use of drug delivery systems (DDS) has been a strategy for the administration of proteins. These systems are biocompatible and biodegradable transporters that exist in the scale of nanometers and are used in the selectived delivery of the drug to the action site by applying targeting ligands to their surface. These systems also protect the drug from possible degradation or denaturation during the transport, thus contributing to a prolonged release at the site of action. There are several types of nanoparticles with different applications and specificities which are dependent on their nanomaterial and properties such as size, shape, hidrophobicity and zeta potential. These properties are controlled during the production of the nanotransporter, with the aim to make the nanoparticle suitable for the intended drug. While in its constitution there are materials, such as lipids, polymers, or inorganic materials such as silica. The application of this technology for the administration of therapeutic proteins and peptides has achieved promising results, such as increased bioavailability and half-life of the drug in circulation in several studies. In the modern days, several drugs based on recombinant proteins have been introduced on the market, in which nanotechnology in applied in their drug delivery systems.
Description
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2020, Universidade de Lisboa, Faculdade de Farmácia.
Keywords
Proteínas Nanotransportador Sistema de veiculação de fármacos Especificidade Nanopartículas Mestrado integrado - 2020