Formulation, Characterization, and Lipolysis Properties of Lycopene-Loaded Self-Emulsifying Delivery Systems Based on Different Lipids

Lycopene is a naturally potent lipophilic antioxidant, which limits its bioavailability for absorption during intestinal digestion. Therefore, this study utilized a self-emulsifying delivery system (SEDS) to enhance the solubility and bioavailability of lycopene and investigated the effects of nonionic surfactant mixtures at varying hydrophilic–lipophilic balance (HLB) values and surfactant-to-oil ratios (SORs) on SEDS using oleic acid (OA), medium-chain triglycerides (MCTs), and sunflower oil (SO) as oil matrices. The resulting water-in-oil-in-water emulsions exhibited droplet sizes (181.70 to 572.27 nm), polydispersity indices (0.29 to 0.86), and ζ-potentials (−22.90 to −53.70 mV), with stability varying according to the type of oil and formulation parameters. Antioxidant activities of SO-based SEDS were higher compared to MCT-based and OA-based ones due to lycopene loading increase. In vitro simulated intestinal digestion revealed differences in lipolysis kinetics, with MCT-based lycopene-loaded SEDS exhibiting enhanced cumulative release and bioaccessibility in the duodenal (1.1–2.1 mEq/g) and jejunal (1.6–2.2 mEq/g) segments. This study revealed a comprehensive strategy encompassing lycopene extracts, SEDS preparation, quality indices, lipolysis dynamics, and proximal intestine solubilization amounts that successfully enhanced lycopene bioavailability. Optimized MCT-based lycopene-loaded SEDS with high HLB (10.72) and SOR (1.00) enhanced hydrophobic bioactive delivery efficiency, offering a novel low-energy strategy for developing functional supplements.