Carrier-Free Silibinin/Sorafenib Microparticles Alleviate Metabolic Dysfunction-Associated Steatotic Liver Disease by Modulating Fatty Acid Metabolism

Introduction Metabolic dysfunction-associated steatotic liver disease (MASLD), characterized by excessive fat accumulation in the liver, is the most prevalent cause of chronic liver disease globally. The clinical use of pharmacological agents such as silibinin and sorafenib is limited due to poor water solubility, low bioavailability, and potential side effects, necessitating innovative therapeutic approaches.Methods In this study, we developed self-assembled, carrier-free microparticles of silibinin and sorafenib (SIL-SOR-MPs) using magnetic stirring and evaluated their therapeutic effects on MASLD both in vitro and in vivo.Results Compared to free SIL and free SOR, SIL-SOR-MPs significantly reduced lipid accumulation in HepG2 cells and effectively alleviated hepatic steatosis and liver damage in mice. Mechanistic investigations further showed that SIL-SOR-MPs more effectively down-regulated lipid synthesis genes and up-regulated genes involved in lipid oxidation.Discussion In summary, our study highlights that carrier-free SIL-SOR-MPs demonstrate the ability to reverse the progression of MASLD and present a promising therapeutic strategy.