Structure
of Chitosan Determines Its Interactions with Mucin
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Abstract
Synthetic
and natural mucoadhesive biomaterials in optimized galenical
formulations are potentially useful for the transmucosal delivery
of active ingredients to improve their localized and prolonged effects.
Chitosans (CS) have potent mucoadhesive characteristics, but the exact
mechanisms underpinning such interactions at the molecular level and
the role of the specific structural properties of CS remain elusive.
In the present study we used a combination of microviscosimetry, zeta
potential analysis, isothermal titration calorimetry (ITC) and fluorescence
quenching to confirm that the soluble fraction of porcine stomach
mucin interacts with CS in water or 0.1 M NaCl (at <i>c</i> < <i>c</i>*; relative viscosity, η<sub>rel</sub>, ∼ 2.0 at pH 4.5 and 37 °C) via a heterotypic stoichiometric
process significantly influenced by the degree of CS acetylation (DA).
We propose that CS–mucin interactions are driven predominantly
by electrostatic binding, supported by other forces (e.g., hydrogen
bonds and hydrophobic association) and that the DA influences the
overall conformation of CS and thus the nature of the resulting complexes.
Although the conditions used in this model system are simpler than
the typical in vivo environment, the resulting knowledge will enable
the rational design of CS-based nanostructured materials for specific
transmucosal drug delivery (e.g., for Helicobacter
pylori stomach therapy)