Engineering the viscoelastic and adhesive properties of mucosa-mimetic poly(vinyl alcohol)/mucin hydrogels to model the small intestinal mucosa

Mucoadhesive formulations can improve the bioavailability of active ingredients in a patient-friendly manner compared to conventional, non-adhesive dosage forms. However, evaluating mucoadhesive performance is highly challenging on ex vivo samples due to the natural variability and storage difficulties of biological samples, thus mucosa-mimetic materials are becoming increasingly important for the robust, in vitro prediction of mucoadhesive properties. In this work, we prepared mucosa-mimetic hydrogels with closer resemblance in adhesive and viscoelastic properties to those of porcine small intestinal mucosa compared to previous models. To this end, we re-designed our previously developed mucin-containing poly(vinyl alcohol) (muc/PVA) hydrogel model, synthesized via the freeze-thaw method. Our approach has two key elements: minimizing the number of freeze-thaw cycles and tailoring the mechanical properties by the mucin content in the hydrogels. The adhesion on the mucosa-mimetic hydrogels was tested by using tablets of mucoadhesive excipients with highly dissimilar physicochemical properties: hydroxypropyl methylcellulose, slightly cross-linked poly(acrylic acid), and chitosan. The model hydrogels were able to differentiate the tablets in terms of their adhesion, and it was also possible to control the strength of adhesion by changing the mucin content of the hydrogels. Furthermore, muc/PVA hydrogels with a specific mucin content (6.5 wt%) displayed satisfactory similarity in viscoelasticity and adhesion towards all polymer tablets to small intestine, thus the studied range of muc/PVA hydrogels can be useful models in early development steps of novel mucoadhesive dosage forms.