**Background:** Selenium (Se) is an essential micronutrient, and organic selenium (e.g., selenium-enriched peptides, SP) offers lower toxicity and higher bioavailability than inorganic forms. However, SP is unstable and easily denatured under oxygen, heat, and alkali. Microencapsulation can protect such bioactive compounds. Electrospraying is a gentle, heat-free technique suitable for encapsulating heat-sensitive substances. Dextran (DX) and whey protein isolate (WPI) are food-grade materials with complementary properties—WPI provides nutrition and biocompatibility, while DX can delay protein dissolution. This study aimed to fabricate DX-WPI-SP ternary composite microcapsules via electrospraying, characterize their physicochemical properties, evaluate antioxidant capacity, and assess controlled release and biocompatibility.
**Methods:** DX-WPI-SP microcapsules were prepared using a high-voltage electrospraying device (DW-N503-1ACDF0 power supply, automatic syringe pump, grounded receiver). The optimized parameters were: 6% DX (w/v), feeding rate 1.0 mL/h, voltage 15 kV, receiving distance 15 cm. WPI content varied from 4% to 8% (w/v). Anhydrous ethanol was used as the receiving solvent. Characterization included optical microscopy, SEM, FTIR, XRD, and TGA/DTG. Antioxidant activity was assessed via DPPH and ABTS radical scavenging assays. Release behavior was studied at pH 2.0, 7.0, and 12.0 over 120 min, and in simulated gastric juice (pepsin, pH 1.2, 2 h) followed by simulated intestinal juice (trypsin/bile, 3 h). Release kinetics were fitted to zero-order, first-order, Higuchi, and Korsmeyer–Peppas models. Cytotoxicity was evaluated in Caco-2 cells using the CCK-8 assay after digestion. All experiments were performed in triplicate; data are mean ± SD, with significance assessed by Duncan’s test (p < 0.05) using SPSS 26.
**Key Results:** Optimized DX-WPI-SP microcapsules had spherical morphology with uniform size distribution. Diameters ranged from ~40.06 μm (DX/WPI/SP 6:4:9) to ~44.22 μm (6:8:9), and loading rates decreased from ~46% to ~37% as WPI increased from 4% to 8%. SEM showed smooth surfaces for pure DX microcapsules, rough/irregular surfaces for DX-WPI, and more bumps/folds for DX-WPI-SP. FTIR confirmed SP loading via hydrogen bonding (redshift from ~3300 to ~3286 cm⁻¹) without new chemical bonds. XRD indicated the microcapsules were mainly amorphous. TGA/DTG showed improved thermal stability of encapsulated SP compared to free SP. Antioxidant assays: DX-WPI-SP microcapsules exhibited ~67.7% of the DPPH/ABTS scavenging activity of free SP, but significantly higher activity than DX or DX-WPI microcapsules alone. Release studies: SP was released rapidly within 10 min (70–80% cumulative release), then plateaued at ~70–85%. Release was faster at lower pH (pH 2.0 > pH 7.0 > pH 12.0). In simulated gastrointestinal conditions, ~90% of SP was released within 120 min. Release kinetics best fit the first-order model at pH 2.0 and the Korsmeyer–Peppas model at pH 7.0 and pH 12.0. Cytotoxicity: Caco-2 cell viability remained >90% even at the highest Se concentration tested (~46 μg/mL), with no significant difference from control (p > 0.05 for all dilutions).
**Clinical Implications:** This study presents a food-grade, electrospray-based microencapsulation system that effectively protects selenium-enriched peptide, enhances its thermal stability, and enables controlled release under gastrointestinal conditions. The negligible cytotoxicity and high biocompatibility suggest potential for developing SP as a safe and effective selenium supplement. The work provides a practical approach for delivering sensitive bioactive peptides in functional foods, though further in vivo studies are needed to confirm bioavailability and efficacy.