A novel strategy for controlled release of sialic acid based on W1/O/W2 emulsion microencapsulation for gut microbiota modulation.

Sialic acid (Neu5Ac) possesses a wide range of bioactivities; however, its instability under acidic conditions prevents it from effectively reaching the intestine. This underscores the urgent need to develop a stable delivery system capable of protecting Neu5Ac from gastric degradation and achieving its controlled release in the intestine. To enhance the stability and achieve controlled release, Neu5Ac was encapsulated within water-in-oil-in-water (W1/O/W2) emulsion-based microcapsules in this work. S2 emulsions featured a "dual-chamber, tri-phase" structure, comprising a Neu5Ac-chitosan fluid gel (inner aqueous phase), maize oil (oil phase), and an external aqueous phase of 13% sodium starch octenyl succinate, 5% β-cyclodextrin, 1.5% sodium caseinate, and 0.5% carboxymethyl cellulose. Microstructural analyses confirmed spherical morphology with core-shell architecture and bimodal droplet distribution (1-10 μm). In addition, S2 emulsions exhibited an encapsulation efficiency (EE) of 92.44%, a zeta potential of -60.80 mV, a Sauter mean diameter (d3,2) of 1.337 μm, shear-thinning behavior and weak gel network stability. S2 emulsions were spray-dried to obtain S2 microcapsules. S2 microcapsules exhibited an EE of 89.43% and a d3,2 of 3.839 μm, while FT-IR and XRD verified physical encapsulation without covalent bonding. In vitro digestion, S2 microcapsules exhibited controlled release behavior during simulated intestinal digestion, with a Neu5Ac release rate of 85.61% after 120 min. In mice, microencapsulated Neu5Ac increased the relative abundance of Akkermansia, Lactobacillus, and Bifidobacterium. This system demonstrates promising potential for the co-delivery and controlled release of Neu5Ac, and shows great promise for expanding its applications in the food industry.