Abstract
Over the past 10 years, the interest in intranasal drug delivery in pharmaceutical R&D has increased. This review article summarises information on intranasal administration for local and systemic delivery, as well as for CNS indications. Nasal delivery offers many advantages over standard systemic delivery systems, such as its non-invasive character, a fast onset of action and in many cases reduced side effects due to a more targeted delivery. There are still formulation limitations and toxicological aspects to be optimised. Intranasal drug delivery in the field of drug development is an interesting delivery route for the treatment of neurological disorders. Systemic approaches often fail to efficiently supply the CNS with drugs. This review paper describes the anatomical, histological and physiological basis and summarises currently approved drugs for administration via intranasal delivery. Further, the review focuses on toxicological considerations of intranasally applied compounds and discusses formulation aspects that need to be considered for drug development.Graphical abstract
Highlights
Nasal administration has been used for therapeutic reasons for centuries
The interest in intranasal drug delivery (INDD) is growing for central nervous system (CNS) indications as in neurodegenerative diseases and other types of CNS disorders, because the blood-brain barrier (BBB) is limiting the bioavailability of drugs after systemic delivery
There is a need for more basic research to understand the anatomy and physiology, and pathologic mechanisms and their influence on each other
Summary
Nasal administration has been used for therapeutic reasons for centuries. As the respiratory tract is a primary contact zone for the environment, it represents a gateway, for infectious particles such as bacteria and viruses and for potential treatments. Crowe et al state that the olfactory nerve axonal transport alone should only take 45 min for an intranasally administered drug to reach the brain [15]; other processes such as endocytosis and exocytosis are not included in these calculations and prolong the time in practice This is based on velocity values measured in an ex vivo study using WGA-HRP and olfactory C-fibres. Prominent examples include oxytocin known for its positive effects on social behaviour and autism [161,162,163] as well as orexin-A improving the CNS hypocretin signalling and olfaction and offering a possible treatment for narcolepsy [164,165,166] Another potential agent for nasal drug delivery is leptin for treating obesity and sleep disorders. The performance depends on the formulation and the patient’s interaction and has to be critically evaluated
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