Hybrid prodrug-nanoassemblies coated by chitosan exerted antioxidant and anti-inflammatory effect on liver fibrosis

The activation and inflammation of hepatic stellate cells (HSCs) promoted the progression of liver fibrosis. The antioxidant and anti-inflammatory therapy can effectively alleviate liver fibrosis. Here, dual prodrug nanoassemblies modified with chitosan (CS/HS-HD NPs) was constructed. The particle size of CS/HS-HD NPs was about 200 nm, which was uniformly dispersed spherical particles, and Zeta potential was positive. The CS/HS-HD NP loaded SLB 3.66 ± 0.04 % and DEX 0.52 ± 0.01 %. In vitro stability and release investigation showed CS/HS-HD NPs had good stability and sustained release characteristics without burst release. These results of in vivo pharmacokinetics, intestinal absorption and in vivo distribution showed that CS/HS-HD NPs had longer t l/2 and larger AUC than other groups (Free drug, HS-HD NPs), which significantly enhanced intestinal absorption and specific accumulation in the liver. In CCl 4 -induced liver fibrosis, CS/HS-HD NPs significantly inhibited the secretion of pro-inflammatory cytokines TNF-α, IL-6 and IL-12, and increased anti-inflammatory cytokines IL-10 level, and then reduce the infiltration of inflammatory cells. The image of liver, HE staining, Masson staining showed CS/HS-HD NPs reduced collagen deposition and liver pathological damage, effectively improved liver fibrosis. Taken together, these findings suggested chitosan coated hybrid prodrug-nanoassemblies could adjust inflammatory cytokines and improve therapeutic effect on liver fibrosis.