Enhanced Gastrointestinal Stability of an Angiotensin-Converting Enzyme Inhibitory Peptide via Alginate-Coated Nanostructured Lipid Carriers and Hydrophobic Ion Pairing

Abstract

Hydrophilic food-derived ACE-inhibitory peptides show poor compatibility with lipid carriers and may exhibit reduced measurable ACE-inhibitory activity during gastrointestinal digestion, limiting their oral food applications. This study aimed to identify a potent peptide from Sophora moorcroftiana seed protein and develop a food-grade delivery strategy combining hydrophobic ion pairing (HIP) with alginate-coated nanostructured lipid carriers (NLCs). Proteomics-guided screening and experimental validation identified MGLPWYR (IC50 = 0.752 μM). Sodium oleate-mediated HIP increased the operationally defined particle-associated peptide fraction from 48.81 ± 0.59% for Peptide-NLC to 75.80 ± 0.37% for HIP–NLC, while Alg–HIP–NLC maintained a comparable value of 76.30 ± 0.50%. After 4 h of simulated intestinal digestion, ACE-inhibitory activity measured in the clarified digest fractions was 25.58%, 54.62%, and 47.62% for free MGLPWYR, HIP–NLC, and Alg–HIP–NLC, respectively. The formulation strategy improved peptide association with the lipid carrier and altered the ACE-inhibitory activity profile during simulated gastrointestinal digestion. These findings support further evaluation of HIP-based lipid carriers for oral delivery of food-derived bioactive peptides.