, Volume 8, Issue 2, pp 581–586 | Cite as

Antihepatotoxic Activity of Liposomal Silibinin

  • Sergey V. Lutsenko
  • Tatiana I. Gromovykh
  • Ivan I. KrasnyukJr
  • Ivan A. Vasilenko
  • Nataliya B. Feldman


The liposomal form of silibinin was obtained, and its antihepatotoxic activity in mice was studied using a model of acute toxic hepatitis caused by injection of carbon tetrachloride or paracetamol. It was shown that the use of the drug in therapy or prevention regimens leads to normalization of levels of transaminases and total protein in the blood of experimental animals. The results of the study showed that liposomal silibinin when administered intravenously shows a more pronounced hepatoprotective effect compared to intragastric administration of free silibinin. Thus, the effectiveness of the therapeutic action of silibinin can be significantly increased by using its liposomal form. Liposomal drug, in contrast to native silibinin, can be injected directly into the blood that significantly increases its bioavailability.


Silibinin Liposomes Drug delivery systems Hepatitis 



The work is performed according to the Russian Government Program of Competitive Growth of I.M. Sechenov First Moscow State University.

Compliance with Ethical Standards

All animal experiments were approved by the All-Russian Research Institute of Medicinal and Aromatic Plants Bioethics Committee.

Conflict of Interest

The authors declare no conflict of interest.


  1. 1.
    Saller, R., Meier, R., & Brignoli, R. (2001). The use of silymarin in the treatment of liver diseases. Drugs, 61, 2035–2063. Scholar
  2. 2.
    Pradhan, S. C., & Girish, C. (2006). Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine. The Indian Journal of Medical Research, 124, 491–504.Google Scholar
  3. 3.
    Abenavoli, L., Capasso, R., Milic, N., & Capasso, F. (2010). Milk thistle in liver diseases: past, present, future. Phytotherapy Research, 24, 1423–1432. Scholar
  4. 4.
    Vargas-Mendoza, N., Madrigal-Santillán, E., Morales-González, A., Esquivel-Soto, J., Esquivel-Chirino, C., García-Luna, Y., González-Rubio, M., Gayosso-de-Lucio, J. A., & Morales-González, J. A. (2014). Hepatoprotective effect of silymarin. World Journal of Hepatology, 6, 144–149. Scholar
  5. 5.
    Wu, J. W., Lin, L. C., Hung, S. C., Chi, C. W., & Tsai, T. H. (2007). Analysis of silibinin in rat plasma and bile for hepatobiliary excretion and oral bioavailability application. Journal of Pharmaceutical and Biomedical Analysis, 45, 635–641. Scholar
  6. 6.
    Bozzuto, G., & Molinari, A. (2015). Liposomes as nanomedical devices. International Journal of Nanomedicine, 10, 975–999. Scholar
  7. 7.
    Daraee, H., Etemadi, A., Kouhi, M., Alimirzalu, S., & Akbarzadeh, A. (2016). Application of liposomes in medicine and drug delivery. Artif Cells Nanomed Biotechnol, 44, 381–391. Scholar
  8. 8.
    Qian, S., Li, C., & Zuo, Z. (2012). Pharmacokinetics and disposition of various drug loaded liposomes. Current Drug Metabolism, 13, 372–395. Scholar
  9. 9.
    Elmowafy, M., Viitala, T., Ibrahim, H. M., Abu-Elyazid, S. K., Samy, A., Kassem, A., & Yliperttula, M. (2013). Silymarin loaded liposomes for hepatic targeting: in vitro evaluation and HepG2 drug uptake. European Journal of Pharmaceutical Sciences, 50, 161–171. Scholar
  10. 10.
    El-Samaligy, M. S., Afifi, N. N., & Mahmoud, E. A. (2006). Increasing bioavailability of silymarin using a buccal liposomal delivery system: preparation and experimental design investigation. International Journal of Pharmaceutics, 308, 140–148. Scholar
  11. 11.
    Ochi, M. M., Amoabediny, G., Rezayat, S. M., Akbarzadeh, A., & Ebrahimi, B. (2016). In vitro co-delivery evaluation of novel pegylated nano-liposomal herbal drugs of silibinin and glycyrrhizic acid (nano-phytosome) to hepatocellular carcinoma cells. Cell Journal, 18, 135–148. Scholar
  12. 12.
    Wang, M., Xie, T., Chang, Z., Wang, L., Xie, X., Kou, Y., Xu, H., & Gao, X. (2015). A new type of liquid silymarin proliposome containing bile salts: its preparation and improved hepatoprotective effects. PLoS One, 10, e0143625. Scholar
  13. 13.
    Dube, D., Khatri, K., Goyal, A. K., Mishra, N., & Vyas, S. P. (2010). Preparation and evaluation of galactosylated vesicular carrier for hepatic targeting of silibinin. Drug Development and Industrial Pharmacy, 36, 547–555. Scholar
  14. 14.
    Maheshwari, H., Agarwal, R., Patil, C., & Katare, O. P. (2003). Preparation and pharmacological evaluation of silibinin liposomes. Arzneimittel-Forschung, 53, 420–427. Scholar
  15. 15.
    Kumar, N., Rai, A., Reddy, N. D., Raj, P. V., Jain, P., Deshpande, P., Mathew, G., Kutty, N. G., Udupa, N., & Rao, C. M. (2014). Silymarin liposomes improves oral bioavailability of silybin besides targeting hepatocytes, and immune cells. Pharmacological Reports, 66, 788–798. Scholar
  16. 16.
    Jillavenkatesa, A., Dapkunas, S. J., & Lum, L.-S. H. (2001). Particle size characterization. Washington: National Institute of Standards and Technology.Google Scholar
  17. 17.
    Reitman, S., & Frankel, S. (1957). A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. American Journal of Clinical Pathology, 28, 56–63.CrossRefGoogle Scholar
  18. 18.
    Lubran, M. M. (1978). The measurement of total serum proteins by the Biuret method. Annals of Clinical and Laboratory Science, 8, 106–110.Google Scholar
  19. 19.
    Szoka, F., & Papahadjopoulos, D. (1978). Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation. Proc Nat Acad Sci USA, 75, 4194–4198. Scholar
  20. 20.
    Jaeschke, H., Gores, G. J., Cederbaum, A. I., Hinson, J. A., Pessayre, D., & Lemasters, J. J. (2002). Mechanisms of hepatotoxicity. Toxicological Sciences, 65(2), 166–176. Scholar
  21. 21.
    Ben-Shachar, R., Chen, Y., Luo, S., Hartman, C., Reed, M., & Nijhout, H. F. (2012). The biochemistry of acetaminophen hepatotoxicity and rescue: a mathematical model. Theoretical Biology & Medical Modelling, 9, 55. Scholar
  22. 22.
    Kamiyama, T., Sato, C., Liu, J., Tajiri, K., Miyakawa, H., & Marumo, F. (1993). Role of lipid peroxidation in acetaminophen-induced hepatotoxicity: comparison with carbon tetrachloride. Toxicology Letters, 66(1), 7–12.CrossRefGoogle Scholar
  23. 23.
    Baer-Dubowska, W., Szaefer, H., & Krajka-Kuzniak, V. (1998). Inhibition of murine hepatic cytochrome P450 activities by natural and synthetic phenolic compounds. Xenobiotica, 28(8), 735–743.CrossRefGoogle Scholar
  24. 24.
    Surai, P. F. (2015). Silymarin as a natural antioxidant: an overview of the current evidence and perspectives. Antioxidants (Basel), 4(1), 204–247. Scholar
  25. 25.
    Allen, T. M., & Cullis, P. R. (2004). Drug delivery systems: entering the mainstream. Science, 303(5665), 1818–1822. Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Biotechnology DepartmentI.M. Sechenov First Moscow State Medical UniversityMoscowRussian Federation
  2. 2.Analytical, Physical and Colloid Chemistry DepartmentI.M. Sechenov First Moscow State Medical UniversityMoscowRussian Federation
  3. 3.Technopark DepartmentI.M. Sechenov First Moscow State Medical UniversityMoscowRussian Federation
  4. 4.All-Russian Research Institute of Medicinal and Aromatic PlantsMoscowRussian Federation

Personalised recommendations