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Novel pterostilbene-loaded pro-phytomicelles: preclinical pharmacokinetics, distribution, and treatment efficacy against acetaminophen-induced liver injury.

A novel pro-phytomicelle formulation with small molecule phytochemicals as nanomaterials was developed for the oral delivery of pterostilbene (PTE) in our previous work. The present report was designed to preclinically evaluate the in vivo oral bioavailability, organ and tissue distribution, as well as the strengthened efficacy against acetaminophen-induced liver damage of this novel formulation, named PTE pro-phytomicelles. After oral administration in rats, an improvement in the area under the curve (AUC)0→t of the PTE pro-phytomicelles (34832.25 vs. 13115.72 ng ml-1 h) and an increase in their maximum plasma concentration (Cmax) (4.940 vs. 2.175 μg ml-1), as compared with those of bare PTE, were observed. The organ and tissue distribution further showed that the PTE pro-phytomicelles could effectively increase the concentration of PTE in all the tested organs and gastrointestinal segments. In the efficacy evaluation, the overdose of Acetaminophen induced severe liver injury in mice, and the oral administration of PTE pro-phytomicelles could efficiently suppress ALT and AST levels in serum, restore histopathological changes, and result in more effective improvement against liver damage via oxidative stress and inflammation cytokine inhibition. The mechanism through which high-mobility group box 1 (HMGB1) signaling was regulated was involved in this treatment. These results reveal that PTE pro-phytomicelles could achieve significantly improved in vivo profiles than bare PTE, and these pro-phytomicelles might provide a new concept and promising therapeutic potential in terms of PTE nanomedicines.