Novel luteolin@pro-phytomicelles: In vitro characterization and in vivo evaluation of protection against drug-induced hepatotoxicity

Abstract

A novel nanoformulation with the small molecule phytochemical dipotassium glycyrrhizinate as a nanomaterial was developed for the oral delivery of luteolin (Lut), a widely used phytochemical, but it suffered from poor water solubility and low oral bioavailability. This novel nanoformulation, named Lut@pro-phytomicelles, can be fabricated with a simple process. Lut@pro-phytomicelles can instantly dissolve into aqueous mediums and formulate through self-assembly a clear phytomicelle solution with a Lut encapsulation efficiency of 99.16 ± 0.90%, a small micelle size of 30.32 ± 0.12 nm, and a narrow polydispersity index of 0.138 ± 0.024. The optimized formulation demonstrated that Lut had solubility in up to 50 mg/ml of water as a result of its encapsulation within DG phytomicelles. Lut@pro-phytomicelles exhibited excellent characteristics, including good storage stability, a fast in vitro release profile, improvement in in vitro antioxidant activity, and high safety potential. In the oral bioavailability evaluation, a shorter Tmax, increased Cmax, and improved AUC0-t were obtained with Lut@pro-phytomicelles when compared to bare Lut. The distribution evaluation further showed that Lut@pro-phytomicelles could effectively increase the concentrations of Lut in all the tested organs and gastrointestinal segments. In the protection efficacy evaluation, 100 mg/kg Lut@pro-phytomicelles demonstrated strong effects against acetaminophen-induced hepatotoxicity. The mechanisms of inhibiting high-mobility group box 1 signaling and suppressing oxidative stress were involved in this strong treatment effect. These results showed that simple but novel Lut@pro-phytomicelles provided a new, promising nano-delivery system for Lut with a significantly improved in vivo profile.