Self-constructed Oleanolic acid Pickering emulsions: Oil-regulated bioavailability with intrinsic lipid inhibition

Self-constructed emulsion interface delivery systems (EIDS) based on hydrophobic bioactives represent a novel delivery strategy. Water-in-oil emulsions structured with oleanolic acid (OA) as the Pickering particle significantly enhance OA bioavailability. To further evaluate the efficacy of the EIDS, this study assessed oil phase composition effects on OA absorption in the emulsion, as well as the digestive absorption characteristics of the emulsion's oil phase. Results demonstrated that OA cellular uptake in the self-constructed emulsion involves a multi-pathway synergistic mechanism, including paracellular transport, clathrin-mediated endocytosis, and lipid raft/caveolae-mediated endocytosis. Among these, LCT-based EIDS significantly increased paracellular permeability, resulting in higher OA bioavailability (26.80 ± 3.03%) in the LCT group compared to the MCT-treated OA group (7.35 ± 2.92%). Concurrently, the lipid digestion and absorption in the emulsion were significantly inhibited, indicating that OA also exerts its own inhibitory effect on lipid digestion and absorption during the delivery process. The results indicate that the mechanism by which OA inhibits lipid digestion may involve its binding to bile salts, thereby reducing the efficiency of pancreatic lipase in acting on lipids. Additionally, OA appears to inhibit the intracellular re-synthesis of triglycerides and the assembly/secretion of chylomicrons, likely through downregulating the mRNA expression of FATP4 , DGAT2 , MGAT2 , and MTP . The enhanced OA bioavailability originates from this unique absorption mechanism, while OA's intrinsic lipid-inhibitory function prevents added lipid burden during oral delivery. This demonstrates self-constructed EIDS as an efficient strategy for hydrophobic phytochemical delivery. • Novel self-constructed emulsion uses OA as both stabilizer and bioactive. • LCT-EIDS enhances OA bioavailability 3.6-fold through increased TJ permeability. • OA reduces lipid absorption by >10% via bile salt binding and key gene suppression. • Self-constructed EIDS reduces the lipid burden while improving triterpenoid delivery.