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Administração de Fármacos do Nariz para o Cérebro e sua Aplicação na Doença de Alzheimer
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Abstract(s)
Há algumas décadas, a esperança média de vida era cerca de metade da atual, devido às condições precárias em que as populações viviam. Com a evolução da ciência, esta tem aumentado de década para década. O facto de as populações viverem por mais tempo é bastante positivo, mas trouxe também o incremento das doenças neurodegenerativas associadas ao envelhecimento natural. Estas doenças afetam as células nervosas cerebrais e, apesar de todo o avanço tecnológico, o cérebro é ainda uma área por explorar. A Doença de Alzheimer é um dos exemplos de doenças neurodegenerativas, sendo a mais prevalente a nível mundial. Crê-se que o seu mecanismo fisiopatológico tenha por base a acumulação de dois tipos de proteínas: a proteína β-amilóide e a proteína tau hiperfosforilada. Não existe atualmente tratamento curativo para esta doença, sendo que a terapêutica disponível tem apenas como finalidade atenuar a sintomatologia inerente à degradação neuronal. Parte da problemática da terapêutica existente prende-se com a via de administração, uma vez que os fármacos administrados por via oral sofrem efeito de primeira passagem, o que resulta na diminuição da sua biodisponibilidade. Além disso, alcançar os locais alvo, localizados no cérebro, requer atravessar a barreira hematoencefálica, o que só é possível com determinadas caraterísticas físico-químicas, como o reduzido tamanho e o equilíbrio entre a lipofilia e a hidrofobia de determinado composto.
Surge assim a necessidade de desenvolver novas estratégias de tratamento que ultrapassem estas limitações. Neste contexto, a administração direta de fármacos do nariz para o cérebro emerge como uma solução bastante promissora. Esta abordagem pressupõe a administração de fármacos por via intranasal, uma vez que é a única via que possibilita a condução direta do fármaco até ao cérebro. Esta condução é possibilitada pelos nervos cranianos, o trigémeo e o olfativo, e pela absorção facilitada na mucosa nasal. Neste contexto, a presente dissertação consiste na revisão bibliográfica de estratégias relacionadas com a administração direta de fármacos da cavidade nasal para o cérebro no âmbito do tratamento da Doença de Alzheimer. Serão focadas em particular técnicas de encapsulação em sistemas lipídicos, e a sua posterior administração pela via nasal, mitigando questões associadas ao efeito sistémico e à barreira hematoencefálica.
A few decades ago, average life expectancy was around half of what it is today, due to the precarious conditions in which populations lived. With the evolution of science, this has increased from decade to decade. The fact that populations live longer is very positive, but it also brought an increase in neurodegenerative disorders associated with natural aging. These diseases affect brain nerve cells and, despite all the technological advances, the brain is still an area to be explored. Alzheimer’s disease is an example of one of the most prevalent neurodegenerative diseases worldwide. It is believed that its pathophysiological mechanisms involve the accumulation of two proteins: β amyloid protein and hyperphosphorylated tau protein. Currently, there is no curative treatment for this disease, and the available therapy aims only to alleviate the symptoms associated with neuronal degradation. Part of the challenge with existing therapy is related to the way medications are administered, since drugs administered orally suffer a first-pass effect, wich results in a decrease in their bioavailability. Furthermore, reaching the brain, where therapeutic targets are located, requires crossing the blood brain barrier, which is only possible for certain compounds with specific characteristics, such as the reduced size and a balance between hydrophobicity and lipophilicity. Therefore, there is a need to develop new treatment strategies that overcome these limitations. In this context, the direct administration of drugs from the nose to the brain emerges as a promising solution. This technique involves the administration of drugs through the nasal route, as it is the only route that allows the drug to be directly transported to the brain. This is made possible by cranial nerves such as the trigeminal and the olfactory nerves, as well as facilitated absorption in the nasal mucosa. In this context, this dissertation consists of a bibliographical review of strategies related to the direct administration of drugs from the nasal cavity to the brain in the treatment of Alzheimer’s Disease. Particular focus will be on encapsulation techniques in lipidic systems and their subsequent administration via the nasal route, mitigating issues associated with the systemic effect and the blood-brain barrier.
A few decades ago, average life expectancy was around half of what it is today, due to the precarious conditions in which populations lived. With the evolution of science, this has increased from decade to decade. The fact that populations live longer is very positive, but it also brought an increase in neurodegenerative disorders associated with natural aging. These diseases affect brain nerve cells and, despite all the technological advances, the brain is still an area to be explored. Alzheimer’s disease is an example of one of the most prevalent neurodegenerative diseases worldwide. It is believed that its pathophysiological mechanisms involve the accumulation of two proteins: β amyloid protein and hyperphosphorylated tau protein. Currently, there is no curative treatment for this disease, and the available therapy aims only to alleviate the symptoms associated with neuronal degradation. Part of the challenge with existing therapy is related to the way medications are administered, since drugs administered orally suffer a first-pass effect, wich results in a decrease in their bioavailability. Furthermore, reaching the brain, where therapeutic targets are located, requires crossing the blood brain barrier, which is only possible for certain compounds with specific characteristics, such as the reduced size and a balance between hydrophobicity and lipophilicity. Therefore, there is a need to develop new treatment strategies that overcome these limitations. In this context, the direct administration of drugs from the nose to the brain emerges as a promising solution. This technique involves the administration of drugs through the nasal route, as it is the only route that allows the drug to be directly transported to the brain. This is made possible by cranial nerves such as the trigeminal and the olfactory nerves, as well as facilitated absorption in the nasal mucosa. In this context, this dissertation consists of a bibliographical review of strategies related to the direct administration of drugs from the nasal cavity to the brain in the treatment of Alzheimer’s Disease. Particular focus will be on encapsulation techniques in lipidic systems and their subsequent administration via the nasal route, mitigating issues associated with the systemic effect and the blood-brain barrier.
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Keywords
Administração intranasal Barreira hematoencefálica Doença de alzheimer Nanopartículas Nariz para o cérebro