Preparation, modification, characterization, and stability evaluation of 5-methyltetrahydrofolate liposomes

As an essential B vitamin, folate participates in one‑carbon metabolism. The 5-methyltetrahydrofolate (5-MTHF) avoids the drawbacks associated with folic acid and native folylpolyglutamate folate in food, thereby emerging as a superior alternative to folate supplement. To enhance the stability and digestibility of 5-MTHF, nanoliposome (NL) was modified using a layer-by-layer self-assembly method with chitosan (CH) and pectin (P). Chitosan–nanoliposome (CH–NL) and pectin–chitosan–nanoliposome (P–CH–NL) were created, each featuring a core–shell structure. P–CH–NL achieved an encapsulation efficiency of 64.62 %, loading efficiency of 1.05 mg/g, and particle size of 285.86 nm. It exhibited better physical stability and 5-MTHF retention (>80 %) under various conditions, including salt and pH variations, as well as oxidative, thermal, fermentation, and UV stress. During in vitro digestion, P–CH–NL protected 5-MTHF until it was released into the small intestine. This study highlighted the application prospects of multilayer liposome-loaded 5-MTHF as a stable, highly digestible folate supplement.