Silybum Marianum-based Nanoformulations for Enhanced Hepatoprotective and Anticancer Activity

Abstract Purpose The poor solubility, low bioavailability, and rapid degradation of bioactive compounds such as silybin and curcumin limit their therapeutic potential. This study aims to develop a novel nanoformulation by coencapsulating silybin and curcumin with Silybum marianum seed extract, a natural encapsulant, to increase their stability, bioavailability, and therapeutic efficacy for hepatoprotection and anticancer applications. Methods Silybin and curcumin were encapsulated via a nanoprecipitation method. The formulation was characterized for its particle size, zeta potential, encapsulation efficiency, and in vitro release kinetics. Molecular docking studies were conducted to evaluate interactions with key proteins (Nrf2, COX-2, TNF-α, P53, and AKT1) involved in oxidative stress, inflammation, and cancer. Antimicrobial activity was assessed against mastitis-related pathogens via the agar well diffusion and broth dilution methods. Cytotoxicity was evaluated in the MCF-7 (breast cancer) and HepG2 (liver cancer) cell lines via the MTT assay. Results The nanoformulation resulted in a mean particle size of 191.00 ± 2.25 nm, a zeta potential of −32.03 ± 1.63 mV, and high encapsulation efficiencies for silybin (85.5 ± 2.1%) and curcumin (82.3 ± 1.8%). Sustained release profiles were observed, with 98.1% and 89.1% cumulative release for silybin and curcumin, respectively, over 48 h. Molecular docking revealed strong binding affinities, particularly for silybin with AKT1 (−11.9 kcal/mol) and for curcumin with COX-2 (−8.4 kcal/mol). The formulation demonstrated enhanced antimicrobial activity, with a minimum inhibitory concentration (MIC) of 20.90 ± 5.20 µg/mL against E. coli , and superior anticancer efficacy, with an IC50 of 81.11 ± 1.95 µg/mL in MCF-7 cells. Conclusion This study presents a novel, natural nanoformulation with dual hepatoprotective and anticancer potential. The use of Silybum marianum seed extract as both a bioactive encapsulant and a therapeutic synergist offers a sustainable and effective alternative to synthetic drug delivery systems, highlighting its potential for clinical applications in liver diseases and cancer therapy. Graphical Abstract