Nanoemulsion based on natural components enables oral liver-targeting delivery of Schizandrol B to enhance liver regeneration after hepatectomy in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality worldwide, with partial hepatectomy (PHx) serving as the primary curative treatment. Schizandrol B (SCHB) has demonstrated significant efficacy in promoting liver regeneration and restoring hepatic function following PHx. However, the clinical application of SCHB faces two critical challenges: poor oral bioavailability and inadequate liver-specific targeting. Here, this study developed a nanoemulsion based on natural components named SCHB@SPC/Gal-BSA/DHA. It effectively overcame the limitations of SCHB by synergizing Gal-BSA-mediated liver-specific targeting and DHA-enhanced intestinal absorption, achieving prolonged gastrointestinal tract retention, 2.03-fold higher oral bioavailability and 7.64-fold greater liver accumulation compared to free SCHB. In both 70% PHx and in situ PHx in HCC models, the nanoemulsion robustly accelerated liver regeneration, evidenced by upregulated proliferation markers via STAT3/YAP activation and normalized bile acids metabolism, ultimately restoring liver mass faster than control. This study demonstrates that the dual-targeted nanoemulsion effectively overcomes the key limitations of SCHB by combining enhanced intestinal absorption with liver-specific targeting. The developed nanoemulsion system not only improves drug delivery efficiency but also significantly promotes liver regeneration after PHx, offering a promising therapeutic approach for postoperative recovery in HCC patients while establishing a platform for future liver-targeted oral drug delivery systems.