Albumin-Based Silibinin Nanocrystals Targeting Activated Hepatic Stellate Cells for Liver Fibrosis Therapy

Abstract

Activated hepatic stellate cells (aHSCs) are critical during the development and progression of liver fibrosis. Once liver fibrosis occurs, aHSCs highly express secreted protein, acidic and rich in cysteine (SPARC), a typical albumin-binding protein. We designed a nano platform, silibinin albumin nanocrystals (SLB-HSA NCs), to target aHSCs for liver fibrosis therapy. The prepared SLB-HSA NCs showed uniform particle size distribution of approximately 60 nm with PDI < 0.15 and high loading efficiency up to 49.4%. Albumin coated on the surface of nanocrystals was demonstrated to increase cellular uptake by aHSCs through SPARC-mediated endocytosis. In addition, SLB-HSA NCs significantly improved the bioavailability compared with free SLB in pharmacokinetic study. Following tail-vein injection, SLB-HSA NCs were massively accumulated in the fibrotic liver and exhibited enhanced antifibrotic effects in hepatic fibrosis mice. Overall, our findings prove the great potential of SLB-HSA NCs in the targeted treatment of liver fibrosis.