Controlling the Interaction between Starchy Polyelectrolyte Layers for Adjusting Protein Release from Nanocapsules in a Simulated Gastrointestinal Tract

Orally delivered bioactive proteins face great challenges in the harsh environment of the upper gastrointestinal tract (GIT) in the field of functional foods based on bioactive proteins. Therefore, it is necessary to design carriers and delivery systems that have the potential to overcome the problem of lower bioaccessibility for protein cargoes. In this work, we present a starchy oral colon-targeting delivery system, capable of improving the release profile of the protein cargoes. The starchy oral colon-targeting delivery system was fabricated using layer-by-layer assembly of starchy polyelectrolytes (carboxymethyl anionic starch and spermine cationic starch) onto the surface of protein nanoparticles via electrostatic interaction. The dynamic change in the interaction between the starchy polyelectrolytes affected the shell aggregation structure and determined the release kinetics of nanocapsules in the GIT. Specifically, the stronger interactions between the starchy layers and the thicker and more compact shell layer kept the nanocapsule intact in the simulated gastric and intestinal fluids, better-protecting the protein from degradation by digestive fluids, thus avoiding the burst release effect in the SGF and SIF. However, the nanocapsule could quickly swell with the decreasing molecular interactions between starchy polyelectrolytes, increasing protein release (63.61%) in the simulated colonic fluid. Therefore, release behaviors of protein cargoes could be appropriately controlled by adjusting the number of deposited layers of pH-sensitive starchy polyelectrolytes on the nanocapsule. This could improve the bioaccessibility of oral targeted delivery of bioactive proteins to the colon.