Hou_2026_Food.Res.Int_233_119041

To improve the bioavailability and bioactivity of phytosterols (PS), soy peptide-based nanogels (SPNs) were prepared by ultrasonic method using peptides with different degrees of hydrolysis (DH) as carriers. The DH was optimized to enhance PS delivery and in vitro cholesterol-lowering activity of SPNs. The results showed that SPNs with moderate DH (MSPN, DH 15.96%) achieved the highest encapsulation efficiency (EE, 80.17%) and intestinal release efficiency (IRE, 57.59%), with an average particle size of 273.95 nm, a polydispersity index (PDI) of 0.245, and a zeta potential of -37.58 mV, indicating favorable stability. Moderate hydrolysis promoted the exposure of hydrophobic groups, increased surface hydrophobicity, and enhanced the conformational flexibility of the peptide chains, which facilitated the interactions between PS and peptides. As the dominant intermolecular forces in MSPN, hydrogen bonds (34%) and hydrophobic interactions (28%) promoted the formation of a stable gel network and ordered secondary structures with increased beta-sheet and alpha-helix contents, thus improving EE of PS. Furthermore, MSPN exhibited a high cholesterol micellar solubility inhibition rate (73.22%) and bile acid binding capacity (66.13%), which was attributed to synergistic effects of cholesterol-lowering amino acids and bioactive peptides released during gastrointestinal digestion. Subsequently, the key bioactive peptide SSPDIFNPQ was identified from MSPN digests; it bound specifically to the active site of cholesterol esterase and inhibited its activity by 61.76% at 40 mg/mL. This study provides a theoretical foundation for the rational design of multifunctional peptide-based delivery systems that simultaneously achieve enhanced delivery efficiency and intrinsic bioactivity.