AbstractsMedical & Health Science

Tese de mestrado integrado, Engenharia Biomédica e Biofísica (Sinais e Imagens Médicas), Universidade de Lisboa, Faculdade de Ciências, 2016 The development of methods for Central Nervous System drug delivery is still a challenge, due to the difficulty to deliver drug molecules across the Blood-Brain barrier that prevents the access of 100% of large-molecule drugs and 98% of small-molecule drugs. Different methods have been tested with the goal to bypass the Blood-Brain Barrier, but they are either invasive, non-targeted or require the formulation of new drugs. We hypothesized that the combination of two methods, Focused Ultrasound and Intranasal delivery, can reduce the disadvantages that other methods present and result in greater overall delivery, improved tissue penetration, and possibly enrichment of the therapeutic agent (i.e. targeting) in the desired location(s) in brain. This pilot study was designed to test the performance characteristics of study designs, measures, procedures, recruitment criteria and operational strategies. By doing an animal model with 12 rats, we achieved a simple and efficient experimental method to apply Focused Ultrasound and Intranasal delivery combined and the only changes done between subjects were related to the quantity given, timings and concentration. Gadolinium enhancement was detected along the olfactory pathway, reaching the main olfactory epithelium in all the rats and it was possible also to visualize flux through the main olfactory bulb also. We also proved that all the intranasal delivered model drugs using Focused Ultrasound (Trypan Blue and Dextrans) bypassed the Blood-Brain Barrier, being in that case delivered in important areas in the brain, in the level of the Rostral Striatum and the Substantia Nigra, targets for Parkinson’s disease. The findings can corroborate the idea that Focused Ultrasound can enhance the delivery of drugs in the brain using Intranasal administration, providing a target outcome and more sensitive, which is valuable in brain applications. As doenças do sistema nervoso como as doenças de Alzheimer e Parkinson fazem parte das principais causas de incapacidade e morte, a nível mundial, estando a incidência das mesmas a aumentar associado a factores como o envelhecimento da população. Existe assim um enorme problema relacionado com a libertação de drogas para processos de controlo de doença nestes pacientes, estando sujeitos à existência de diversos mecanismos de protecção das estruturas inerentes ao sistema nervoso central. Um dos mais importantes é a barreira hematoencefálica que constitui um desafio a ultrapassar aquando da entrega de drogas terapêuticas, impedindo a entrada de cerca de 100% das substâncias com maior peso molecular e de 98% para as restantes. Diversos métodos têm sido desenvolvidos de modo a contornar esta barreira, apresentando porém limitações relacionadas com o facto de serem invasivos, terem uma baixa especificidade, alta toxicidade, sendo assim necessária a procura de outras técnicas. A utilização de ultra-sons em… Advisors/Committee Members: Matela, Nuno Miguel de Pinto Lobo e, 1978-, McDannold, Nathan.