1. Highly bioavailable silibinin nanoparticles inhibit HCV infection
- Author
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Cheng Jeng Tai, Chun Ching Lin, Chueh Yao Chung, Ming Hong Yen, Chih Chan Lin, Liang Tzung Lin, Ching Hsuan Liu, Wen Chan Hsu, D. Lorne Tyrrell, Chen Jei Tai, Shun Pang Chang, Justin Shields, Christopher D. Richardson, and Alagie Jassey
- Subjects
0301 basic medicine ,Male ,Silibinin ,Hepacivirus ,Pharmacology ,Antioxidants ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Drug Delivery Systems ,Pharmacokinetics ,In vivo ,Oral administration ,medicine ,Flavonolignan ,Animals ,Humans ,Cells, Cultured ,Hepatitis ,Life Cycle Stages ,Chemistry ,Gastroenterology ,Hepatitis C ,medicine.disease ,Bioavailability ,Rats ,030104 developmental biology ,Silybin ,Hepatocytes ,030211 gastroenterology & hepatology ,Nanospheres ,Silymarin - 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 ( 97% efficiency and increasing the compound9s solubility by >75%. Treatment with SB-NP efficiently restricted HCV cell-to-cell transmission, suggesting that they retained silibinin9s 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-NP9s 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.
- Published
- 2016