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Nanoparticles as carrier systems for protein delivery
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As terapias com recurso a proteínas têm apresentado um desenvolvimento significativo ao longo das últimas décadas, constituindo novas opções terapêuticas para um grande número de doenças. Contudo, a entrega bem sucedida das proteínas continua a ser uma tarefa difícil, uma vez que estas podem sofrer degradação enzimática na circulação sistémica, apresentam baixa permeabilidade celular e, consequentemente, biodisponibilidade reduzida, limitando a sua aplicação. Nesta revisão da literatura são revisitados conceitos-chave na área da nanomedicina, bem como várias abordagens desenvolvidas para o transporte e entrega de péptidos e proteínas. Os nanotransportadores são especificamente desenhados para proteger os fármacos da biodegradação, controlar a sua libertação, permitir atingir de forma eficiente os orgãos e tecidos alvo e reduzir a citotoxicidade. Um nanotransportador ideal deve ser biocompatível e biodegradável, apresentar uma eficiência de encapsulação elevada e uma grande capacidade de manter a estrutura e a actividade da proteína. Para além disso, a sua produção deve ser simples e reprodutível, deve apresentar opções de administração clinicamente relevantes e ser economicamente viável. Propriedades como o tamanho, a forma e a superfície devem ser tidas em conta no desenvolvimento de novos nanotransportadores, dado que têm um papel fundamental na estabilidade, especificidade em relação ao alvo e cinética de libertação dos fármacos, que são aspectos determinantes para a sua eficiência. Existem vários tipos de nanotransportadores, quer orgânicos quer inorgânicos, incluindo nanopartículas de lípidos sólidos, lipossomas, nanoparticulas de polímeros, nanopartículas víricas, nanopartículas de sílica mesoporosa, nanopartículas metálicas e nanopartículas magnéticas. A toxicidade destas particulas é altamente determinada pelas suas propriedades físico-químicas, uma vez que estas influenciam a forma como as partículas interagem com as células. O conhecimento destas interaçóes permite o desenvolvimento de nanopartículas mais seguras. Foram desenvolvidos e introduzidos na prática clínica vários nanomedicamentos e existem muitos outros que se encontram ainda em fase de investigação. No entanto, os numerosos problemas técnicos, associados à falta de protocolos padrão para a caraterização fisico-química e fisiológica/biológica de novas formulações, têm comprometido o desenvolvimento e aprovação de diversas terapias. Apesar de todos os problemas que ainda necessitam de resolução, as nanopartículas com proteínas constituem uma grande promessa como agentes terapêuticos, aumentando a biodisponibilidade e controlando a libertação das proteínas, ao mesmo tempo que as direccionam de forma eficiente para os órgãos e tecidos alvo.
Protein-based therapies have significantly developed over the past decades, providing new therapeutic options for a wide range of diseases. However, successful protein delivery remains a challenging task, since they can be degraded by enzymes in systemic circulation, present low cell permeability and have poor bioavailability, thereby limiting their clinical application. This review revisits the fundamental concepts in the field of nanomedicine, as well as several approaches developed for peptide and protein delivery. Engineered nanocarriers are specifically designed to protect drugs from biodegradation, control their release and clearance, and allow efficient targeting of organs and tissues, with reduced cytotoxicity. An ideal nanocarrier must show biocompatibility, biodegradability, elevated encapsulation efficiency, high capacity to keep protein structure and bioactivity, simple and reproducible production, clinically relevant administration options, and economic feasibility. Properties such as size, shape and surface must be considered in the design of a new nanocarrier, as they play a significant role in the nanoparticles’ stability, targeting specificity and drug release kinetics, thus directly affecting their therapeutic efficacy. There are a vast number of nanocarrier’s types from organic to inorganic structures, including solid lipid nanoparticles, liposomes, polymeric nanoparticles, virus-based nanoparticles, mesoporous silica nanoparticles, metallic nanoparticles and magnetic nanoparticles. The toxicity of these particles is highly determined by their physical and chemical properties, since they influence how the particles interact with cells. Thus, understanding these interactions can lead to the development of safer nanoparticles. Several nanomedicines have been developed and commercially approved for clinical use, with many more being currently under clinical investigation. However, the numerous technical issues coupled with the lack of standard protocols for physicochemical and physiological/biological characterization of new formulations have compromised the development and approval of many therapies. Despite all the issues that still need to be addressed, protein-loaded nanoparticles hold great promise as new therapeutic agents for targeted therapies, increasing protein bioavailability, controlling their release and efficiently targeting organs and tissues.
Protein-based therapies have significantly developed over the past decades, providing new therapeutic options for a wide range of diseases. However, successful protein delivery remains a challenging task, since they can be degraded by enzymes in systemic circulation, present low cell permeability and have poor bioavailability, thereby limiting their clinical application. This review revisits the fundamental concepts in the field of nanomedicine, as well as several approaches developed for peptide and protein delivery. Engineered nanocarriers are specifically designed to protect drugs from biodegradation, control their release and clearance, and allow efficient targeting of organs and tissues, with reduced cytotoxicity. An ideal nanocarrier must show biocompatibility, biodegradability, elevated encapsulation efficiency, high capacity to keep protein structure and bioactivity, simple and reproducible production, clinically relevant administration options, and economic feasibility. Properties such as size, shape and surface must be considered in the design of a new nanocarrier, as they play a significant role in the nanoparticles’ stability, targeting specificity and drug release kinetics, thus directly affecting their therapeutic efficacy. There are a vast number of nanocarrier’s types from organic to inorganic structures, including solid lipid nanoparticles, liposomes, polymeric nanoparticles, virus-based nanoparticles, mesoporous silica nanoparticles, metallic nanoparticles and magnetic nanoparticles. The toxicity of these particles is highly determined by their physical and chemical properties, since they influence how the particles interact with cells. Thus, understanding these interactions can lead to the development of safer nanoparticles. Several nanomedicines have been developed and commercially approved for clinical use, with many more being currently under clinical investigation. However, the numerous technical issues coupled with the lack of standard protocols for physicochemical and physiological/biological characterization of new formulations have compromised the development and approval of many therapies. Despite all the issues that still need to be addressed, protein-loaded nanoparticles hold great promise as new therapeutic agents for targeted therapies, increasing protein bioavailability, controlling their release and efficiently targeting organs and tissues.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2019
Palavras-chave
Nanotransportadores Nanoterapias Nanopartículas Proteina Entrega. Mestrado Integrado - 2019