Non-Invasive Strategies for Nose-to-Brain Drug Delivery

Abstract

Intranasal drug administration is a promising method for delivering drugs directly to the brain. Animal studies have described pathways and potential brain targets, but nose-to-brain delivery and treatment efficacy in humans remains debated. We describe the proposed pathways and barriers for nose-to-brain drug delivery in humans, drug properties that influence central nervous system delivery, clinically tested methods to enhance absorption, and the devices used in clinical trials. This review compiles the available evidence for nose-to-brain drug delivery in humans and summarizes the factors involved in nose-to-brain drug delivery.

Keywords: Bioavailability; Biodistribution; Devices; Intranasal administration; Nose-to-brain.

Figure 1:

Nose-to-brain delivery pathways. The target region for effective nose-to-brain drug delivery is the olfactory epithelium in the upper nasal cavity. This region contains olfactory nerve cells which bypass the BBB & provide direct access to the brain & CSF. Nose-to-brain transport is depicted by the solid lines; clearance is depicted by the dotted lines. The box shows transport through the following routes: perivascular pump, bulk flow, lymphatic drainage, & endoneural transport through the olfactory & trigeminal nerves. Minimal amounts of intranasally administered drug may enter the CNS via carotid artery branches; the main limiting barrier for this route is vascular endothelium permeability. Systemic absorption through the nasal mucosa is not significant.