Comparative Pharmacokinetics of Lutein and Zeaxanthin from Phospholipid, Liposomal, and MCT Formulations in SD Rats

Background: Lutein and zeaxanthin (LZ) are macular xanthophyll carotenoids with antioxidant and blue-light filtering properties, but their oral bioavailability is limited. Lipid-based delivery systems may enhance absorption. Methods: We compared four single-dose LZ delivery systems in male Sprague–Dawley rats: (G1) LZ in medium-chain triglyceride (MCT) oil; (G2) LZ in MCT + phosphatidylcholine (PC); (G3) LZ in MCT + phosphatidylserine (PS); (G4) LZ in liposomal powder. Following an overnight fast, each group (n = 6) received an oral gavage of the assigned formulation. Serial blood samples were collected up to 24 h post-dose. Plasma lutein + zeaxanthin concentrations were quantified by a validated LC–MS/MS method. Non-compartmental pharmacokinetic (PK) parameters were computed (Phoenix WinNonlin®), and one-way ANOVA was used to make inter-group comparisons on ln-transformed metrics with Dunnett’s post hoc tests. Results: The PS-complexed formulation (G3) yielded the highest LZ exposure (mean C_max 69.63 ± 0.78 ng/mL; AUC_0-t 620.23 ± 16.41 ng·h/mL), significantly exceeding the MCT oil control (G1: 52.54 ± 0.70 ng/mL; 494.51 ± 13.70 ng·h/mL; p < 0.001). The PC-enriched oil (G2) and liposomal powder (G4) also produced higher C_max and AUC than G1 (p < 0.01). No differences in elimination half-life (t1/2 ≈ 8 h) were observed between formulations. Conclusions: Phospholipids, especially with PS, substantially improve lutein and zeaxanthin systemic availability versus MCT oil alone. PS-based lipid complexes appear particularly effective, supporting their use in ocular-health formulations to maximise xanthophyll bioavailability.