Abstract
The nasal cavity is an attractive route for both local and systemic drug delivery and holds great potential for access to the brain via the olfactory region, an area where the blood–brain barrier (BBB) is effectively absent. However, the olfactory region is located at the roof of the nasal cavity and only represents ~5–7% of the epithelial surface area, presenting significant challenges for the deposition of drug molecules for nose to brain drug delivery (NTBDD). Aerosolized particles have the potential to be directed to the olfactory region, but their specific deposition within this area is confounded by a complex combination of factors, which include the properties of the formulation, the delivery device and how it is used, and differences in inter-patient physiology. In this review, an in-depth examination of these different factors is provided in relation to both in vitro and in vivo studies and how advances in the fabrication of nasal cast models and analysis of aerosol deposition can be utilized to predict in vivo outcomes more accurately. The challenges faced in assessing the nasal deposition of aerosolized particles within the paediatric population are specifically considered, representing an unmet need for nasal and NTBDD to treat CNS disorders.
Highlights
There has been some progress in drug delivery systems (DDS) for treatment for neurological disorders
The olfactory region is the uppermost region in the nasal cavity exclusively connecting the external environment to the brain, unimpeded by the blood–brain barrier (BBB)
The olfactory region is the uppermost region in the nasal cavity, which exclusively connects the external environment to the brain, unimpeded by the BBB (Figure 1) [13]
Summary
There has been some progress in drug delivery systems (DDS) for treatment for neurological disorders. The use of cell culture models is a common in vitro approach in the study of nasal and NTB drug delivery These include primary cells such as reconstructed human nasal epithelium [40,41], porcine respiratory and olfactory cells [42], or cell lines such as RPMI. The enormous development in 3D printing technologies such as stereolithography (SLA), fused deposition modeling (FDM), and selective laser sintering (SLS) and their promising applications in the healthcare sector [53], alongside the advances in qualitative and quantitative analytical methods, have enabled building explicit nasal replicas as practical and efficient tools for in vitro evaluation of nasal formulations and delivery devices, and they could provide valid preliminary data for clinical trials [54]. E.g., human nasal epithelium, porcine respiratory and olfactory cells
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