Fonseca, Leonor CancelaLopes, JoaoVieira, JoaoViegas, ClaudiaOliveira, Claudia S.Hartmann, Rafael P.Fonte, Pedro2021-09-082021-09-082021-042190-393Xhttp://hdl.handle.net/10400.1/17024The Alzheimer's disease is a neurodegenerative condition with severe consequences interfering with patient quality of life. It is characterized as a progressive and irreversible brain disorder hampering memory and thinking, affecting the capacity to perform daily tasks leading to physical and cognitive incapacitation. The conventional treatment occurs by the oral route, but it presents relevant drawbacks such as low bioavailability, fast metabolism, limited brain exposure, and undesirable side effects. The intranasal route has been proposed as a promising alternative to deliver drugs and improve the Alzheimer's disease treatment. Still, there is not a clear alternative delivery system available in the market with advantageous bioavailability and safety. The aim of this review is to perform an overview on the strategies for drug intranasal delivery for Alzheimer's disease treatment. The advantages and disadvantages of this delivery route and the delivery systems developed so far are discussed. A special focus is given on the use of permeation enhancers, the types of intranasal drug delivery devices, as well as possible toxicity concerns.engNanoparticleProteinPermeation enhancerBlood-brain barrierCentral nervous systemNeurodegenerativeInstruments & Instrumentation; Research & Experimental Medicine; Pharmacology & Pharmacyjournal article10.1007/s13346-021-00940-7