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

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 (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.

Original languageEnglish
Pages (from-to)1853-1861
JournalGut
Volume66
Issue number10
DOIs
Publication statusPublished - Oct 2017

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Nanoparticles
Infection
Hepatitis C
Solubility
Biological Availability
Antiviral Agents
Hepatocytes
Flavonolignans
Pharmacokinetics
Antioxidants
Life Cycle Stages
Free Radicals
Oral Administration
Rodentia
Oxidative Stress
silybin
Clinical Trials
Viruses
Safety
Costs and Cost Analysis

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Liu, C. H., Lin, C. C., Hsu, W. C., Chung, C. Y., Lin, C. C., Jassey, A., ... Lin, L. T. (2017). Highly bioavailable silibinin nanoparticles inhibit HCV infection. Gut, 66(10), 1853-1861. https://doi.org/10.1136/gutjnl-2016-312019

Highly bioavailable silibinin nanoparticles inhibit HCV infection. / Liu, Ching Hsuan; Lin, Chun Ching; Hsu, Wen Chan; Chung, Chueh Yao; Lin, Chih Chan; Jassey, Alagie; Chang, Shun Pang; Tai, Chen Jei; Tai, Cheng Jeng; Shields, Justin; Richardson, Christopher D.; Yen, Ming Hong; Tyrrell, D. Lorne J; Lin, Liang Tzung.

In: Gut, Vol. 66, No. 10, 10.2017, p. 1853-1861.

Research output: Contribution to journalArticle

Liu, CH, Lin, CC, Hsu, WC, Chung, CY, Lin, CC, Jassey, A, Chang, SP, Tai, CJ, Tai, CJ, Shields, J, Richardson, CD, Yen, MH, Tyrrell, DLJ & Lin, LT 2017, 'Highly bioavailable silibinin nanoparticles inhibit HCV infection', Gut, vol. 66, no. 10, pp. 1853-1861. https://doi.org/10.1136/gutjnl-2016-312019
Liu CH, Lin CC, Hsu WC, Chung CY, Lin CC, Jassey A et al. Highly bioavailable silibinin nanoparticles inhibit HCV infection. Gut. 2017 Oct;66(10):1853-1861. https://doi.org/10.1136/gutjnl-2016-312019
Liu, Ching Hsuan ; Lin, Chun Ching ; Hsu, Wen Chan ; Chung, Chueh Yao ; Lin, Chih Chan ; Jassey, Alagie ; Chang, Shun Pang ; Tai, Chen Jei ; Tai, Cheng Jeng ; Shields, Justin ; Richardson, Christopher D. ; Yen, Ming Hong ; Tyrrell, D. Lorne J ; Lin, Liang Tzung. / Highly bioavailable silibinin nanoparticles inhibit HCV infection. In: Gut. 2017 ; Vol. 66, No. 10. pp. 1853-1861.
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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 (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.",
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AU - Hsu, Wen Chan

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AU - Lin, Chih Chan

AU - Jassey, Alagie

AU - Chang, Shun Pang

AU - Tai, Chen Jei

AU - Tai, Cheng Jeng

AU - Shields, Justin

AU - Richardson, Christopher D.

AU - Yen, Ming Hong

AU - Tyrrell, D. Lorne J

AU - Lin, Liang Tzung

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N2 - 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.

AB - 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.

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