Mucosal Delivery of RNAi Therapeutics - RNA Interference from Biology to Therapeutics - page 97

Fig. 5.1 Schematic representation of nanoparticle uptake across mucosal epithelium. ( a ) The
mucosal surfaces lining the respiratory, gastrointestinal and genitourinary tracts and eyes. ( b ) The
mucosal epithelial border restricts penetration of luminal particulates ( right ) through a combina-
tion of overlying mucus composed of a lower steady layer (dark) and an upper layer (light), tight
cellular junctions and ciliary clearance. Exploitation of mucoadhesive and mucopermeable parti-
cles allows cellular uptake across mucosal surfaces ( left ). ( c ) Particles diffusing through the net-
work of mucin fi bres

[ 16 ] and to facilitate continuous exchange of nutrient, water and gases. Mucus has
macroscopic properties of a gel and exhibits non-Newtonian rheological behaviour
[ 17, 18 ]. It is composed of ions, glycoproteins (termed mucins), proteins, lipids,
DNA and cellular debris [ 18 ]. The mucins are extended 0.5-40-MDa molecules that
are produced and secreted by goblet cells. It has a two-layer composition composed
of a lower steady-state layer in contact with the epithelium and a mobile outer layer.
Mucus site variations have evolved to suit the role performed at particular sites.

5.2.1.1 Site Variations

Mucus thickness, rate of renewal and pH are properties that can vary between tis-
sues. The mucus layer thickness determines the accessibility to the underlying
epithelium and depends on both luminal conditions and functional requirements of
the underlying tissue. The layer thickness varies along the human gastrointestinal
tract with the thickest layer in the stomach (~50-450 m m) [ 19 ] and in the colon