Silica-installed redox nanoparticles enable effective oral silymarin therapy for liver fibrosis

Liver fibrosis is a chronic pathological condition caused by repeated or sustained liver injury, for which effective pathological treatments remain limited. Silymarin, a hydrophobic compound with anti-inflammatory, antioxidant, and antifibrotic properties, has shown therapeutic potential. However, its clinical application is restricted by poor aqueous solubility and low gastrointestinal (GI) bioavailability. In this study, we developed silica-containing redox nanoparticles (siRNP) as an oral nanocarrier system to improve the delivery of silymarin to the liver. Silymarin-loaded siRNP (Sil@siRNP) formed stable nanoparticles with a diameter of approximately 50 nm and a narrow size distribution, significantly enhancing drug solubility and stability under GI-mimicking conditions. Cellular uptake studies in RAW264.7 macrophages demonstrated efficient nanoparticle internalization. Following oral administration in mice, Sil@siRNP markedly increased hepatic accumulation of silymarin, suggesting improved bioavailability. Importantly, in a carbon tetrachloride (CCl₄)-induced liver fibrosis model, treatment with Sil@siRNP significantly reduced collagen deposition, serum liver injury markers, and expression of fibrogenic factors compared with free silymarin. No observable systemic toxicity was detected. These results demonstrate that siRNP is an effective oral nanoplatform for enhancing the therapeutic efficacy of hydrophobic drugs and highlight the potential of Sil@siRNP as a promising strategy for the treatment of liver fibrosis.