Structure of Chitosan Determines Its Interactions with Mucin

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 c < c*; relative viscosity, η(rel), ∼ 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).

Chitosan as a non-viral co-transfection system in a cystic fibrosis cell line

“…This may offer the conformational adaptation to CS necessary to complex efficiency the nucleic acids. This is consistent with our previous studies on CS-mucin systems (Menchicchi et al, 2014). Moreover, chitosans with a Mw ~ 20 kDa have been shown to bind and protect completely the nucleic acid from enzymatic degradation (Köping-Höggård et al, 2004).…”

“…Among the main features that this biopolymer convenes is that it is a well-established biocompatible and biodegradable natural polymer. Besides, chitosan is able to establish ionic, hydrogen, and hydrophobic bonding with negatively charged chains of mucin, the structural component of mucus fluids (Menchicchi et al, 2014). All these properties, place chitosan as a potential alternative to administrate drugs to or through the lung.…”

“…Chitosan exhibits several properties that makes it in an interesting material for pharmaceutical formulations. It induces low cytotoxicity, is biocompatible, biodegradable, and mucoadhesive (Rinaudo, 2006;Younes and Rinaudo, 2015;Menchicchi et al 2014). These properties along with its polycationic character make of chitosan a potential unique candidate as a gene delivery system.…”

Biophysical Analysis of the Molecular Interactions between Polysaccharides and Mucin

“…the degree of acetylation) also played a significant role. 8 However, negatively-charged polysaccharides such as alginates, 9 pectins 10 and poly(acrylic acid) 11 also show mucoadhesive properties, indicating that electrostatic interactions are not solely responsible. Mucin forms a complex macromolecular network carrying reactive functional groups (e.g.…”

Mucoadhesion and mucosa-mimetic materials—A mini-review

“…This 195 causes nonpolar regions of macromolecules to aggregate, lowering the surface area accessible to water. This effect has been seen experimentally when studying the interaction of chitosan and mucin by isothermal titration calorimetry (Menchicchi et al, 2014). In addition to hydrophobic effects between mucin and mucoadhesive, the lyophilicity of mucoadhesives affects their affinity for aqueous solutions, so colloids with relatively poor colloidal stability may be driven onto the mucosa 200 more readily.…”