Exploring a new free-standing polyelectrolyte (PEM) thin film as a predictive tool for drug-mucin interactions:...

The main objective of the present work was to design a biomimetic free-standing multilayered PEM film, constructed by the layer-by-layer (LbL) assembly approach, based on natural biopolymers and intended to recreate the complex mucus-mimetic matrices in order to provide mechanistic insights into biophysical interactions between drugs and the physiological gel-forming mucin network of mucus that covers the mucosal epithelia named as(CS/ALG)/(PGM) PEM film. The obtained results indicate that mucin may delay or increase drug precipitation on the mucus layer, depending on specific drug-mucin interactions driving drug supersaturation or drug crystallization phenomena. It was found that the drug lipophilicity characteristics governed the mucin binding degree, which had an influencing role on the drug translocation across this gel-like hydrogel. Moreover, the ionization of these drugs did not have a significant role on the drug binding ability to mucin as much as the lipophilicity properties did. The (CS/ALG)/(PGM) PEM film may be a promising tool to routine testing drug-mucus interactions to evaluate biophysical interactions between this protective barrier of the organism against different drug therapeutic products or external aggressive agents, leading to the optimization of drug delivery products or drugs for particular disease states.