Hedgehog (Hh) and peroxisome proliferator-activated receptor gamma (PPAR-γ) are major signaling pathways involved in the pathogenesis of liver fibrosis. Since Hh inhibitor, vismodegib (GDC) and PPAR-γ agonist, rosiglitazone (RSG) have poor water solubility, our objective was to formulate biodegradable polymeric nanoparticles encapsulating GDC and RSG for treating liver fibrosis.