title: Highly bioavailable silibinin nanoparticles inhibit HCV infection.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ching-Hsuan
authors.initials: CH
authors.lastname: Liu
authors.affiliation: School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.|Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chun-Ching
authors.initials: CC
authors.lastname: Lin
authors.affiliation: School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Wen-Chan
authors.initials: WC
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chueh-Yao
authors.initials: CY
authors.lastname: Chung
authors.affiliation: Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan.
authors.forename: Chih-Chan
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Alagie
authors.initials: A
authors.lastname: Jassey
authors.affiliation: School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Shun-Pang
authors.initials: SP
authors.lastname: Chang
authors.affiliation: Department of Chinese Medicine, Taipei Medical University Hospital, Taipei, Taiwan.|Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chen-Jei
authors.initials: CJ
authors.lastname: Tai
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.|Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Cheng-Jeng
authors.initials: CJ
authors.lastname: Tai
authors.affiliation: Li Ka Shing Institute of Virology, Edmonton, Alberta, Canada.
authors.forename: Justin
authors.initials: J
authors.lastname: Shields
authors.affiliation: Department of Microbiology & Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.|Department of Pediatrics and Canadian Center for Vaccinology, Izaak Walton Killam Health Centre, Halifax, Nova Scotia, Canada.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Richardson
authors.affiliation: Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Yen
authors.affiliation: Li Ka Shing Institute of Virology, Edmonton, Alberta, Canada.
authors.forename: D Lorne J
authors.initials: DLJ
authors.lastname: Tyrrell
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Liang-Tzung
authors.initials: LT
authors.lastname: Lin
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D002478:Cells, Cultured; D016503:Drug Delivery Systems; D016174:Hepacivirus / Q000187:drug effects* / Q000472:pathogenicity; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D008018:Life Cycle Stages / Q000187:drug effects; D008297:Male; D054118:Nanospheres; D051381:Rats; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D012838:Silymarin; D000077385:Silybin
keywords: ANTIVIRAL THERAPY; HCV; HEPATITIS C