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Highly bioavailable silibinin nanoparticles inhibit HCV infection
  1. Ching-Hsuan Liu1,
  2. Chun-Ching Lin2,3,
  3. Wen-Chan Hsu2,
  4. Chueh-Yao Chung3,
  5. Chih-Chan Lin4,
  6. Alagie Jassey1,5,
  7. Shun-Pang Chang2,
  8. Chen-Jei Tai6,7,
  9. Cheng-Jeng Tai8,9,
  10. Justin Shields10,
  11. Christopher D Richardson11,12,
  12. Ming-Hong Yen3,
  13. D Lorne J Tyrrell10,
  14. Liang-Tzung Lin1,5
  1. 1 Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
  2. 2 School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
  3. 3 Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
  4. 4 Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
  5. 5 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
  6. 6 Department of Chinese Medicine, Taipei Medical University Hospital, Taipei, Taiwan
  7. 7 Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
  8. 8 Division of Hematology and Oncology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
  9. 9 Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
  10. 10 Li Ka Shing Institute of Virology, Edmonton, Alberta, Canada
  11. 11 Department of Microbiology & Immunology, Dalhousie University, Halifax, Nova Scotia, Canada
  12. 12 Department of Pediatrics and Canadian Center for Vaccinology, Izaak Walton Killam Health Centre, Halifax, Nova Scotia, Canada
  1. Correspondence to Dr Liang-Tzung Lin, Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, No. 250, Wu-Hsing Street, Taipei 11031, Taiwan; ltlin{at}tmu.edu.tw

Abstract

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 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.

  • HCV
  • HEPATITIS C
  • ANTIVIRAL THERAPY

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