Co-Encapsulation of Curcumin and Fucoxanthin With Multilayer Structural Nanoparticles: In Vitro Programmed Sequential Release Behavior and In Vivo Bioavailability Studies.

Food-grade co-delivery systems with programmed sequential release properties allow for sequential delivery of two bioactives to different sites in the gastrointestinal tract (GIT), improving the bioavailability of the two bioactives in vivo, which has become an emerging field of research. In this paper, multilayer structural nanoparticles (MSNPs) possessing programmed sequential release properties were constructed on the basis of the structural design principle for the co-encapsulation of curcumin (Cur) and fucoxanthin (FUC) with gliadin, carboxymethyl konjac glucomannan, and chitosan hydrochloride using the layer-by-layer self-assembly technique. The programmed sequential release behavior was investigated by in vitro digestion models. It was demonstrated that Cur located in the outer layer of MSNPs relies on a concurrent release mechanism involving diffusion and erosion in simulated gastric fluid. The release of FUC located in the inner layer is primarily driven by diffusion. A large amount of Cur was released in simulated intestinal fluid and driven by the erosive mechanism. Further, FUC was released in large quantities, and its release was governed by erosion in simulated colonic fluid under the influence of β-mannanase. This work reveals a programmed switch from diffusion to erosion as MSNPs transit through different GIT segments, which has rarely been addressed in previous co-delivery systems. Notably, it was confirmed by in vivo animal models that MSNPs increased the bioavailability of the outer layer bioactives and reduced the biodistribution of the inner layer bioactives in the upper GIT. The in-depth study of the programmed sequential release behavior is important for expanding the application of MSNPs in food-grade co-delivery systems.