Development of novel formulations for mucosal delivery of protein ...

(d) pH of environment; the pH of the external environment influences the ionization of the
functional group(s), affecting the charge distribution on the polymer chains. As discussed
earlier, mucoadhesion property depends on the presence of these functional groups and
therefore a change in the pH of the external environment may impact on the mucoadhesive
property. A typical example is the excellent mucoadhesive property of chitosan (cationic
polyelectrolyte) in alkaline or neutral environment (Park et al., 1989)
(e) Method of drying; apart from the above factors, Grabovac et al., (2005) found that the
method of drying is an important factor influencing the mucoadhesive potential of polymeric
formulations. Lyophilisation of thiolated chitosan polymers at pH 3 produced greater
mucoadhesion than other polymers that were dried by casting from organic solvents and air
dried. On the other hand, polyacrylates showed improved mucoadhesion when precipitated in
neutral sodium salts.
1.3.3.3 Mucin
The protein based material, mucin, is the main component of mucus and plays a
significant role in the mucoadhesive characteristics of chitosan and chitosan derivatives
(Fefelova et al., 2007; Sogias et al., 2008). The mucosa layer is made up of mucus secreted by
the goblet cells (glandular columnar epithelial cells) and is a viscoelastic fluid. It lines the
visceral organs, which are exposed to the external environment, including the alimentary
canal/ gastrointestinal (oral cavity, stomach and intestines), respiratory and genitourinary
tracts. The main components constituting the mucosa are water and mucin, which together
constitute > 99 % of the total composition of the mucus and of this greater than 95 % is water
(Roy et al., 2009). The other components present in mucus include proteins, lipids and
mucopolysaccharides. The gel-like structure of the mucus can be attributed to the
intermolecular entanglements of the mucin glycoproteins along with the non-covalent
interactions (e.g. hydrogen, electrostatic and hydrophobic bonds) which results in the
formation of a hydrated gel-like structure and explains the viscoelastic nature of the mucus
(Andrew et al., 2009).
Mucins (Figure 1.6) are a family of high molecular weight (anionic polyelectrolytes),
heavily glycosylated proteins (glycoconjugates) produced by epithelial tissues. Many
epithelial cells produce mucin, but gel-forming mucins are produced primarily in the goblet or
mucous cells of the tracheobronchial, gastrointestinal, and genitourinary tracts. In goblet cells,
mucins are stored intracellularly in mucin granules from which they can be quickly secreted
upon external stimuli.