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

Abstract

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.