This study aimed to prepare a nanoemulsion vehicle to improve the oral bioavailability of hesperetin. The pseudo-ternary phase diagrams and the RSM were used to optimize nanoemulsion parameters. Compared with hesperetin suspension, the AUC 0-t and C max of nanoemulsion were increased by 5.67-fold and 2.64-fold, respectively. The proportion of lymphatic transport reached 87.72%, the cumulative absorption amount of jejunum, ileum, and duodenum increased by 1.1-fold, 1.92-fold, and 1.5-fold, respectively. The results implied that hesperetin nanoemulsion could effectively improve the bioavailability of hesperetin by increasing lymphatic transport and enhancing intestinal permeability. Therefore, nanoemulsion is a potential method to improve the bioavailability of hesperetin, which has strong practicability.

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