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Background  Non-alcoholic fatty liver disease (NAFLD) is a chronic disease that causes excessive hepatic lipid accumulation. Reducing hepatic lipid deposition is a key issue in treatment and inhibition of NAFLD evolution. Silymarin is a potent hepatoprotective agent; however, it has low oral bioavailability due to its poor aqueous solubility and low membrane permeability. Unfortunately, few studies have addressed the development of convenient oral nanocarriers that can efficiently deliver silymarin to the liver and enhance its lipid-lowering effect. We designed silymarin-loaded lipid polymer hybrid nanoparticles containing chitosan (CS-LPNs) to improve silymarin bioavailability and evaluated their lipid-lowering effect in adiponutrin/patatin-like phospholipase-3 I148M transgenic mice, an NAFLD model.    Results  Compared to chitosan-free nanoparticles, CS-LPNs showed 1.92-fold higher uptake by fatty liver cells. Additionally, CS-LPNs significantly reduced TG levels in fatty liver cells in an in vitro lipid deposition assay, suggesting their potential lipid-lowering effects. The oral bioavailability of silymarin from CS-LPNs was 14.38-fold higher than that from suspensions in rats. Moreover, compared with chitosan-free nanoparticles, CS-LPNs effectively reduced blood lipid levels (TG), improved liver function (AST and ALT), and reduced lipid accumulation in the livers of mice in vivo. Reduced macrovesicular steatosis in pathological tissue after CS-LPN treatment indicated their protective effect against liver steatosis in NAFLD.    Conclusions  CS-LPNs enhanced oral delivery of silymarin and exhibited a desirable lipid-lowering effect in a mouse model. These findings suggest that CS-LPNs may be a promising oral nanocarrier for NAFLD therapeutics.    Electronic supplementary material  The online version of this article (10.1186/s12951-018-0391-9) contains supplementary material, which is available to authorized users.

Chitosan-functionalized lipid-polymer hybrid nanoparticles for oral delivery of silymarin and enhanced lipid-lowering effect in NAFLD