Advanced alginate- nutriosomes for enhanced oral delivery of fermented Echium amoenum polyphenols

Echium amoenum, a highly valued medicinal plant in Iran, is rich in polyphenols. Microbial fermentation can improve the bioavailability of its phenolic compounds, which are otherwise limited (5-10%), by releasing them from the plant cell wall. Moreover, incorporating these bioactive compounds in phospholipid vesicles can further maximize their biological efficacy. This study developed a combined approach using lactic acid fermentation with Lactiplantibacillus plantarum and phospholipid-based nanocarriers to optimize the delivery of E. amoenum extract. Fermented extract (50 mg/mL) was successfully incorporated into liposomes, nutriosomes, and advanced alginate-nutriosomes, as confirmed by cryo-TEM and FTIR analyses. All vesicles were nanosized (105-124 nm), negatively charged (~ - 56 mV), and homogeneously dispersed (PDI ≤ 0.19) with high loading efficiencies (> 90%). They remained stable under simulated saliva, gastric, and intestinal conditions and exhibited controlled release. In vitro assays demonstrated biocompatibility and protective effects on stressed Caco-2 cells. Overall, alginate-nutriosomes represent a promising nanocarrier for oral administration of fermented E. amoenum extract.