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

Abstract

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.

Research progress in brain-targeted nasal drug delivery

“…In addition, the interstitial fluid surrounding the olfactory nerve bundle is connected to the cerebrospinal fluid (CSF) in the subarachnoid space, and supporting and basal cells can differentiate into new olfactory neurons and other cell types. The lamina propria of the olfactory and respiratory areas contain an abundance of blood and lymphatic vessels that extend to the lymph nodes deep within the neck ( Shrewsbury, 2023 ).…”

Nose-to-Heart Approach: Unveiling an Alternative Route of Acute Treatment

“…Historically, nasal administration was primarily used for symptomatic relief, prophylaxis, or treatment of local nasal diseases. However, in recent years, the nasal mucosa has evolved into a promising route for systemic and nose-to-brain drug delivery, which takes advantage of its unique structural, physiological, and histological features [17]. The nasal cavity's total area is approximately 150-160 cm 2 , with a volume capacity of 15 to 20 mL [18].…”

An Overview of Proprietary Vehicles/Bases for Topical Compounding Medicines and Cosmetics

“…Compounded medicines are unique, tailor-made products for a patient that take into account not only their therapeutic needs but also their individual characteristics, enhancing the success of the treatment. They are prepared based on a physicians' prescription, or a formulary or pharmacopoeia, and formulated and dispensed under the responsibility of a pharmacist, either in community or hospital pharmacies [48,49].…”

“…Compounded medicines in general can overcome the standardization of pharmaceutical industrial products and may solve several patient problems in obtaining their medication [48,50]:…”