Highly bioavailable silibinin nanoparticles inhibit HCV infection

作者：Ching‐Hsuan Liu, Chun‐Ching Lin, Wen-Chan Hsu, Chueh-Yao Chung, Chih‐Chan Lin, Alagie Jassey, Shun-Pang Chang, Chen‐Jei Tai, Cheng-Jeng Tai, Justin Shields, Christopher D. Richardson, Ming‐Hong Yen, D. Lorne Tyrrell, Liang Lin · 发表于：Gut · 年份：2016 · DOI：10.1136/gutjnl-2016-312019 · 被引用次数：52 · 研究领域：Silymarin and Mushroom Poisoning、Hepatitis C virus research、Curcumin's Biomedical Applications

OBJECTIVE: Silibinin is a flavonolignan that is well established for its robust antiviral activity against HCV infection and has undergone several clinical trials for the management of hepatitis C. Despite its potency, silibinin suffers from poor solubility and bioavailability, restricting its clinical use. To overcome this limitation, we developed highly bioavailable silibinin nanoparticles (SB-NPs) and evaluated their efficiency against HCV infection. DESIGN: SB-NPs were prepared using a nanoemulsification technique and were physicochemically characterised. Infectious HCV culture systems were used to evaluate the influence of SB-NP on the virus life cycle and examine their antioxidant activity against HCV-induced oxidative stress. The safety profiles of SB-NP, in vivo pharmacokinetic studies and antiviral activity against infection of primary human hepatocytes were also assessed. RESULTS: SB-NP consisted of nanoscale spherical particles (<200 nm) encapsulating amorphous silibinin at >97% efficiency and increasing the compound's solubility by >75%. Treatment with SB-NP efficiently restricted HCV cell-to-cell transmission, suggesting that they retained silibinin's robust anti-HCV activity. In addition, SB-NP exerted an antioxidant effect via their free radical scavenging function. Oral administration of SB-NP in rodents produced no apparent in vivo toxicity, and pharmacokinetic studies revealed an enhanced serum level and superior biodistribution to the liver compared with no...