Highly bioavailable silibinin nanoparticles inhibit HCV infection

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 J. Tyrrell, Liang Tzung Lin

研究成果: 雜誌貢獻文章同行評審

33 引文 斯高帕斯(Scopus)


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 (SBNPs) 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 HCVinduced 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 non-modified silibinin. Finally, SB-NP efficiently reduced HCV infection of primary human hepatocytes. Conclusions Due to SB-NP's enhanced bioavailability, effective anti-HCV activity and an overall hepatoprotective effect, we suggest that SB-NP may be a cost-effective anti-HCV agent that merits further evaluation for the treatment of hepatitis C.

頁(從 - 到)1853-1861
出版狀態已發佈 - 10月 2017

ASJC Scopus subject areas

  • 消化內科


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