Leveraging bile acid transporters for enhanced liver targeting and anti-alcoholic efficacy of tectoridin via liposomal delivery

Objective This study focused on improving the delivery of tectoridin, an anti-alcoholic compound from Pueraria flower, which suffers from poor solubility and low bioavailability when taken orally. To address this, we designed a biomimetic liposome system that targets the liver by harnessing the body's natural bile acid transport pathways.Significance Successful clinical translation of many insoluble natural products, including tectoridin, is limited by their unfavorable pharmacokinetics. A liver-targeted strategy utilizing physiological transporters offers a promising means to enhance hepatic delivery and therapeutic efficacy, thereby addressing a critical hurdle in the development of plant-derived pharmaceuticals.Methods Following bioactivity-guided isolation and identification of tectoridin, cholic acid-functionalized liposomes (LPs-tectoridin) were designed to actively target hepatocyte-specific transporters (NTCP/OATPs). The formulation was optimized and characterized for particle size, encapsulation efficiency, and in vitro dissolution. Pharmacokinetic, tissue distribution, and pharmacodynamic evaluations were performed in a rat model of ethanol-induced intoxication and liver injury.Results The optimized liposomes exhibited a mean particle size of 157.55 ± 0.23 nm, a high encapsulation efficiency (>85%), and significantly improved the dissolution rate of tectoridin. In vivo, LPs-tectoridin increased the oral bioavailability (AUC0–24) by 2.11-fold and enhanced hepatic accumulation by 3-fold compared to free tectoridin. The formulation demonstrated superior anti-intoxication and hepatoprotective effects, notably reducing serum ALT and AST levels by 49.95% and 35.20%, respectively, and elevating hepatic SOD activity by 2.04-fold.Conclusions This study not only confirms tectoridin as a principal anti-alcoholic constituent but also establishes a robust liver-targeted liposomal platform that harnesses intrinsic bile acid transport pathways. The strategy significantly improves the solubility, bioavailability, and therapeutic performance of tectoridin, offering a viable approach for enhancing the delivery of poorly soluble natural products in drug development.

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