Transmucosal Nasal Drug Delivery: Systemic Bioavailability of ...

2. Impact of anatomy and physiology on transmucosal nasal drug delivery
gel layer
sol layer
mucus layer
ciliated cell
basement membrane
with neurosecretory cells
Non-ciliated cell
with microvilli
goblet cell
basal cell
Figure 2-2: Respiratory epithelium. The respiratory epithelium is covered by a mucus
layer (gel and sol layer) and the cell types arising from the basement membrane are:
ciliated and non-ciliated cells (with microvilli), goblet cell, and basal cell. Modified after
[Sakane et al., 1991].
2.2.2 Mucus and mucociliary clearance
The goblet cells and the submucosal glands secrete about 20 ml to 40 ml mucus per day [Quraishi
et al., 1998]. The mucus layer protects the underlying tissue from various environmental influences
and the metabolic effects of enzymes. The mucus layer and hairs in the anterior nose filter 80% of
particles larger than 12.5 µm out from the inhaled air stream [Jones 2001]. The pH of the mucus
layer varies from 5.5 to 6.5 in adults and from 5.0 to 7.0 in infants [Arora, et al. 2002].
The principal component of the mucus is water (90-95%) containing mucin (2%), electrolytes (1%),
proteins (1%, mainly albumin, immunoglobulins, and lysozymes), and lipids [Merkus et al., 1998;
Schipper et al., 1991]. Small molecules not interacting with the components of the mucus layer
diffuse freely through the water network of the mucous gel. Khanvilkar et al. demonstrated that for
many compounds, nasal mucus layer adds as little additional resistance as an unstirred water layer
of equal thickness [Khanvilkar et al., 2001].
The mucus layer consists of two films with different rheological properties, a preciliary layer (sol
layer) and a more viscous upper layer (gel layer) covering the tips of the cilia. Responsible for the
rheological properties are two forms of mucin; soluble mucin and membrane bound mucin. Soluble
mucin forms viscous gels by intermolecular disulfide bridges [Khanvilkar, et al. 2001].
The sol layer with low viscosity is slightly less thick than the length of an extended cilium (5 µm to
10 µm). The extended cilia dip into the gel layer and, with effective beats, transports the layer to the
nasopharynx. During the recovery stroke, the cilia move backward through the sol layer. In the
Katja Suter-Zimmermann Page 19 of 188 University of Basel, 2008