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Oral exposure to lipophilic plant bioactives depends on lipid digestion and enterocyte handling. Long-chain fatty acids and monoacylglycerols can be re-esterified and assembled with apolipoprotein B48 into chylomicrons, creating a route through intestinal lymph that differs from portal delivery. Food-grade lipid nanocarriers may alter this pathway by changing lipid digestion, micellar solubilization, cellular uptake, and chylomicron secretion, yet evidence for lymphatic transport is often inferred from bioaccessibility or plasma exposure rather than measured directly. This review evaluates how triglyceride chain length, unsaturation, lipid physical state, emulsifier interfaces, food matrices, and processing shape the digestive transformation of nanoemulsions and lipid particles into mixed colloids and substrates for enterocyte lipid processing. It compares nanoemulsions, nanostructured lipid carriers, liposomes, and related systems, with attention to the distinction between intact-particle uptake and cargo incorporation into endogenous lipoproteins. Static and dynamic digestion, epithelial models, lymph-duct cannulation, chylomicron-associated analyte measurements, and human pharmacokinetics are considered as distinct evidence tiers. The synthesis identifies which design claims are supported by direct lymph measurements and which remain mechanistic hypotheses. A framework aligns lipid composition and cargo chemistry with the intended portal or lymphatic exposure pathway. By treating endogenous chylomicron assembly as a testable design target, this review distinguishes a route-specific mechanism from gains in solubilization, epithelial uptake, or plasma exposure alone.
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Khalil et al. (2026) studied this question.
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