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).

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Mucoadhesive materials adhere persistently to mucosal surfaces. A mucoadhesive delivery system could therefore facilitate the controlled release of drugs and optimize their bioavailability in mucosal tissues. Polysaccharides are the most versatile class of natural polymers for transmucosal drug delivery. We used microviscosimetry to explore the mucoadhesion of a library of polysaccharide families with diverse structural characteristics as a first step towards the rational design of mucoadhesive polysaccharide-based nanoformulations. Here we show that the magnitude of deviation between the viscosity of mixed polysaccharide-mucin solutions and the corresponding individual stock solutions can indicate underlying molecular interactions. We found that nonlinear monotonic curves predicted a correlation between the magnitude of interaction and the ability of polysaccharide coils to contract in the presence of salt (i.e. chain flexibility). Charge-neutral polysaccharides such as dextran and Streptococcus thermophilus exopolysaccharide did not interact with mucin. Synchrotron small-angle X-ray scattering (SAXS) data supported the previously described structural features of mucin. Furthermore, high-q scattering data (i.e. sensitive to smaller scales) revealed that when mucin is in dilute solution (presumably in an extended conformation) in the presence of low-Mw alginate, its structure resembles that observed at higher concentrations in the absence of alginate. This effect was less pronounced in the case of high-Mw alginate but the latter influenced the bulk properties of mucin-alginate mixtures (e.g. hydrodynamic radius and relative viscosity) more prominently than its low-Mw counterpart.

The present review is aimed at elucidating relatively new aspects of mucoadhesion/mucus interaction and related phenomena that emerged from a Mucoadhesion workshop held in Munster on 2-3 September 2015 as a satellite event of the ICCC 13th-EUCHIS 12th. After a brief outline of the new issues, the focus is on mucus description, purification, and mucus/mucin characterization, all steps that are pivotal to the understanding of mucus related phenomena and the choice of the correct mucosal model for in vitro and ex vivo experiments, alternative bio/mucomimetic materials are also presented. Then a selection of preparative techniques and testing methods are described (at molecular as well as micro and macroscale) that may support the pharmaceutical development of mucus interactive systems and assist formulators in the scale-up and industrialization steps. Recent applications of mucoadhesive systems (including medical devices) intended for different routes of administration (oral, gastrointestinal, vaginal, nasal, ocular, and intravesical) and for the treatment of difficult to treat pathologies or the alleviation of symptoms are described.