In vitro passive permeability of propranolol across a chitosan/alginate/mucin free-standing multilayers film

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental (SAFE); 2019

In this work we reported an in vitro permeability assay by using a biomimetic chitosan (CHI)/alginate (ALG)/mucin (MUC) free-standing multilayers film, fabricated by layer-by-layer (LbL) assembly, to predict the in vivo intestinal passive permeability behavior of propranolol (PRO).The CHI/ALG/MUC free-standing multilayers film was designed by functionally mimicking the gut mucosa because they are natural polymers mimic the extracellular matrix components of tissues, while MUC is the main component of the mucus that covers most of the mucosal epithelia and plays a fundamental role in the permeability profiles of drugs, either favoring or impairing their absorption, as drugs administrated through the mucosa will first have to pass the mucus layer.In order to study the interaction between the mucus layer and PRO, permeability studies were performed by assembled the CHI/ALG free-standing multilayers films with or without MUC adsorbed into the film surface. It was found that MUC had not a significant effect on the PRO permeability behavior (p = 0.974). After the PRO permeability tests, films were analyzed by SEM, circular dichroism (DC) and by measurement their contact angles.SEM images of films without MUC showed the presence of the adsorbed drug on the film surface. On the other hand, it was found that PRO produced a structural conformation change of the MUC adsorbed into films from a globular structure to a flat conformation. These results were confirmed by the DC study, where it was clearly observed the conformational change of the MUC by the PRO. Contact angle measurements revealed a different surface wettability behavior of films, being films CHI-ending hydrophobic. In contrast, this film changed its surface to very hydrophilic after into contact with PRO.Results allow concluding that PRO interacts with MUC, affecting the structural conformation of the glycoprotein, without producing a significant effect on the permeability behavior of PRO.