Development of Saikosaponin D Liposome Nanocarrier with Increased Hepatoprotective Effect Against Alcoholic Hepatitis Mice.

Abstract

The mortality rate of ethanol induced liver disease has substantially raised to alert level with an increasing use of alcohol, but development of definite hepatoprotective drug is still challenging. The efficacy of Saikosaponin D, one of the natural herbal medicine has been studied in different diseases. Nonetheless, its clinical application is restricted by poor bioavailability, stability and solubility. This study sought to develop a Saikosaponin D loaded liposome via thin film hydration method. The surface morphology, encapsulation efficiency and drug loading capacity were detected with transmission electron microscopy and HPLC, in vitro dissolution was via dialysis method, but efficacy and safety evaluation was through pharmacokinetics, while the assessment of hepatoprotective activity on alcohol induced acute hepatitis mice models was conducted. The optimized liposomes showed significant greater therapeutic effect on liver, through decreased serum levels of alanine transaminase (ALT) and aspartate transaminase (AST), malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), total cholesterol (TC) and triglyceride (TG) in liver homogenate. In contrast, levels of glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) were increased significantly. Pathological study exhibited remarkable alteration of hepatitis liver architecture to almost normal state after administration of Saikosaponin D liposome. The increased hepatoprotective effect of Saikosaponin D liposome was observed during the attenuation of alcoholic hepatitis in mice, which might be ascribable to the anti-oxidative and anti-inflammatory properties of the drug. This study provides a theoretical basis for developing advanced system of Saikosaponin D delivery for the promotion of the therapeutic effects of the liposome against various kinds of diseases.