Impact of yeast cell wall incorporation on the mucoadhesion, stability, oral permeability and release profile of alginate/whey protein beads loaded with insulin

This study aimed to evaluate the impact of incorporating yeast cell wall (YCW) into alginate/whey protein (ALG/WP) particles as a strategy to improve oral insulin delivery. Insulin-loaded particles were produced by an extrusion-gelation process with or without YCW, and their physicochemical, mucoadhesive, and permeability properties were assessed in vitro, ex vivo, and in vivo. The inclusion of YCW increased the viscosity of the polymeric solution, resulting in more cohesive particles and a significant reduction in insulin loss during coating. Encapsulation efficiencies ranged from 65 to 99%. However, YCW did not significantly affect particle size or the release mechanism, which remained diffusion-controlled. Although YCW-containing beads exhibited enzyme inhibitory and mucoadhesive properties, insulin protection against enzymatic degradation was similar to that of control beads. YCW moderately enhanced insulin permeability in Caco-2 cell monolayers without cytotoxicity, consistent with a reversible reduction of transepithelial electrical resistance. This effect did not translate into a measurable increase in insulin absorption in ex vivo duodenum or in vivo duodenal administration, indicating that its contribution as an absorption enhancer is limited under physiologically complex conditions.