Solid lipid type and ratio modulate hydrophobic component bioavailability: synergistic control of lipolysis,...

Efficient oral utilization of hydrophobic bioactives remains a major challenge for functional food development. Nanostructured lipid carriers (NLCs) are promising delivery systems, yet how solid lipid type and solid-to-liquid lipid (S:L) ratio jointly determine their gastrointestinal fate remains unclear. We systematically compared glycerol 1,3-distearate (GDS)- and beeswax (BW)-based NLCs across S:L ratio using emodin (E) as model compound. Moderate solid lipid fractions reduced intestinal aggregation and improved mucus penetration, while excessive solid lipid promoted flocculation and hindered absorption. GDS-based NLCs showed higher micellization and transmucosal transport at low-to-medium ratios, yielding higher in vivo bioavailability. BW-based NLCs exhibited higher colloidal stability and mucus penetration but suffered limited bioavailability due to reduced lipolysis. Results reveal that digestive behavior and absorption efficiency of NLCs are co-determined by lipid chemistry and formulation ratio, highlighting the importance of rational lipid selection to balance micellization and mucosal interactions. This work provides practical guidance for tailoring food-grade lipid nanocarriers to maximize nutrient absorption.