Solubility-permeability interplay of a supersaturated lutein delivery system constructed by glycosylated stevioside and hydroxypropyl-methylcellulose

This study investigated the solubilizing capacity of glycosylated stevioside/hydroxypropyl-methylcellulose (stevia-G-HPMC) complexes with varying mass ratios on lutein. The impact on the steady-state flux and permeability coefficient of intracellular lutein was also explored through the construction of a Caco-2 cellular transport model. The results indicated that the equilibrium solubility of lutein linearly increased with an increase in stevia-G amount. The stability constants of the ternary system surpassed those of the binary system. Molecular dynamics simulation revealed a tight and stable structure in lutein supersaturated complexes. Meanwhile, lutein-stevia-G-HPMC complexes demonstrated superior cumulative penetrations, with the peak P_app (AP → BL) value being (3.24 ± 0.89) × 10^-5 cm·s^-1. There was a slight decrease in P_app (BL → AP), which improved the forward transport of lutein. Highly soluble lutein in aqueous environments saturated the extracellular transport proteins on the AP side of cell membranes, thereby maintaining the high permeability transport. Notably, the permeability trend of lutein in Caco-2 cells negatively correlated with the equilibrium solubility and matched the single exponential growth model. When the mass ratio of lutein, stevia-G and HPMC was 1:21:5, the solubility-permeability trade-off of lutein was effectively maintained.