The Upper Nasal Space: Option for Systemic Drug Delivery, Mucosal Vaccines and "Nose-to-Brain".

Sino-nasal disease is appropriately treated with topical treatment, where the nasal mucosa acts as a barrier to systemic absorption. Non-invasive nasal delivery of drugs has produced some small molecule products with good bioavailability. With the recent COVID pandemic and the need for nasal mucosal immunity becoming more appreciated, more interest has become focused on the nasal cavity for vaccine delivery. In parallel, it has been recognized that drug delivery to different parts of the nose can have different results and for "nose-to-brain" delivery, deposition on the olfactory epithelium of the upper nasal space is desirable. Here the non-motile cilia and reduced mucociliary clearance lead to longer residence time that permits enhanced absorption, either into the systemic circulation or directly into the CNS. Many of the developments in nasal delivery have been to add bioadhesives and absorption/permeation enhancers, creating more complicated formulations and development pathways, but other projects have shown that the delivery device itself may allow more differential targeting of the upper nasal space without these additions and that could allow faster and more efficient programs to bring a wider range of drugs-and vaccines-to market.