Per Gisle Djupesland, M.D.
Drug Deliv. and Transl. Res.
Intuitively, the nose offers easy access to a large mucosal surface well suited for drug- and vaccine delivery. However, factors related to the nasal anatomy, physiology and aerodynamics that can severely limit this potential, have historically been challenging to address. The most recent FDA guidance for nasal devices provides detailed guidelines for in vitro testing of the physical properties such as in vitro reproducibility and accuracy of plume characteristics and dose uniformity of mechanical liquid spray pumps and pressurized metered-dose inhalers (pMDIs) for nasal use . The guidance primarily addresses in vitro testing of nasal sprays and pressurized aerosols for local action. The reference to in vivo performance is limited to the recommendation of minimizing the fraction of respirable particles below 9 μm in order to avoid lung inhalation of drugs intended for nasal delivery. Thus, although important as measures of the quality and reliability of the spray pump and pMDI mechanics, these in vitro tests do not necessarily predict the in vivo particle deposition, absorption, and clinical response . Furthermore, the guidance offers no or limited guidance on nasal products for systemic absorption and for alternative dispensing methods like drops, liquid jets, nebulized aerosol, vapors, and powder formulations. Finally, it does not address aspects and challenges related to the nasal anatomy and physiology that are highly relevant for the device performance in the clinical setting like body position, need for coordination, and impact of airflow and breathing patterns at delivery.
The mechanical properties of different modes of aerosol generation are already well described in depth in a previous publication . The anatomy and physiology of the nasal airway has also recently been summarized in an excellent recent review . The aim of this paper is to take a step further by reviewing the characteristics of existing and emerging nasal delivery devices and concepts of aerosol generation from the perspective of achieving the clinical promise of nasal drug and vaccine delivery. Focus is put on describing how the nasal anatomy and physiology present substantial obstacles to efficient delivery, but also on how it may be possible to overcome these hurdles by innovative approaches that permit realization of the therapeutic potential of nasal drug delivery. Specific attention is given to the particular challenge of targeted delivery of drugs to the upper narrow parts of the complex nasal passages housing the middle meatus where the sinuses openings are located, as well as the regions innervated by the olfactory nerve and branches of the trigeminal nerve considered essential for efficient “nose-to-brain” (N2B) transport.