Drug Delivery and Translational Research

, Volume 9, Issue 5, pp 968–979 | Cite as

Mesoporous silica nanoparticles, a safe option for silymarin delivery: preparation, characterization, and in vivo evaluation

  • Sarah S. Nasr
  • Maha M. A. Nasra
  • Heba A. HazzahEmail author
  • Ossama Y. Abdallah
Original Article


The present work aimed to prepare silymarin-loaded mesoporous silica nanoparticles (MSNs) and to assess the system’s dissolution enhancement ability on the pharmacodynamic performance of silymarin as a hepatoprotective agent. For this purpose, a soft-templating technique was used to prepare silymarin-loaded MSNs. The loaded MSNs were further characterized for their particle size, zeta potential, surface properties, and in vitro drug dissolution testing. In addition, differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were also carried out. DSC and specific surface area data confirmed deposition of silymarin in an amorphous state in MSNs’ pores. In vitro drug dissolution testing displayed enhanced dissolution rate of silymarin upon loading on MSNs compared with the free drug. Paracetamol-induced rat model of liver injury was used for the in vivo study. Plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), total proteins, liver homogenate content of thiobarbituric acid reactive species (TBARS), or lactate dehydrogenase (LDH) were assessed for all animal groups, treated and control ones. Based on parameters indicative of liver function, our results showed that the oral use of silymarin loaded onto MSNs at a dose of 250 mg/kg is significantly superior to free silymarin. Moreover, prolonged administration of the formulation had no evident toxicity on rats.


Mesoporous silica Nanoparticles Toxicity Silymarin Liver function 



The authors would like to express their gratitude to the Institute of Post Graduate Studies and Research, the dean Prof. Mokhtar Youssef, and Dr. Alaa Fathy Ibrahim for their assistance with the preliminary in vivo experiments. They would also like to extend their sincere appreciation to Prof. Hanan el Goweli, Department of Pharmacology, Faculty of Pharmacy, Alexandria University, for her valuable assistance with the in vivo experiment.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Vallet-Regi M, Rámila A, del Real RP, Pérez-Pariente J. A new property of MCM-41: drug delivery system. Chem Mater. 2001;13(2):308–11.Google Scholar
  2. 2.
    Xu W, Riikonen J, Lehto V-P. Mesoporous systems for poorly soluble drugs. Int J Pharm. 2013;453(1):181–97.Google Scholar
  3. 3.
    Hoshikawa Y, Yabe H, Nomura A, Yamaki T, Shimojima A, Okubo T. Mesoporous silica nanoparticles with remarkable stability and dispersibility for antireflective coatings. Chem Mater. 2010;22(1):12–4.Google Scholar
  4. 4.
    Slowing II, Trewyn BG, Giri S, Lin VSY. Mesoporous silica nanoparticles for drug delivery and biosensing applications. Adv Funct Mater. 2007;17(8):1225–36.Google Scholar
  5. 5.
    Hata H, Saeki S, Kimura T, Sugahara Y, Kuroda K. Adsorption of taxol into ordered Mesoporous silicas with various pore diameters. Chem Mater. 1999;11(4):1110–9.Google Scholar
  6. 6.
    Wang Y, Zhao Q, Han N, Bai L, Li J, Liu J, et al. Mesoporous silica nanoparticles in drug delivery and biomedical applications. Nanomedicine. 2015;11(2):313–27.Google Scholar
  7. 7.
    Yao X, Niu X, Ma K, Huang P, Grothe J, Kaskel S, et al. Graphene quantum dots-capped magnetic mesoporous silica nanoparticles as a multifunctional platform for controlled drug delivery, magnetic hyperthermia, and photothermal therapy. Small. 2017;13(2):1602225.Google Scholar
  8. 8.
    Tamanoi F, et al. In vivo tumor suppression efficacy of mesoporous silica nanoparticle-based drug delivery system: enhanced efficacy by folate modification. Nanomedicine in Cancer; 2017. Pan Stanford. p. 241–260.Google Scholar
  9. 9.
    Sarah PH, et al. The biocompatibility of mesoporous silicates. Biomaterials. 2008;29(30):4045–55.Google Scholar
  10. 10.
    Paris JL, Cabañas MV, Manzano M, Vallet-Regí M. Polymer-grafted mesoporous silica nanoparticles as ultrasound-responsive drug carriers. ACS Nano. 2015;9(11):11023–33.Google Scholar
  11. 11.
    Zhang Y, Wang J, Bai X, Jiang T, Zhang Q, Wang S. Mesoporous silica nanoparticles for increasing the oral bioavailability and permeation of poorly water soluble drugs. Mol Pharm. 2012;9(3):505–13.Google Scholar
  12. 12.
    Popat A, Jambhrunkar S, Zhang J, Yang J, Zhang H, Meka A, et al. Programmable drug release using bioresponsive mesoporous silica nanoparticles for site-specific oral drug delivery. Chem Commun. 2014;50(42):5547–50.Google Scholar
  13. 13.
    Dixit N, Baboota S, Kohli K, Ahmad S, Ali J. Silymarin: a review of pharmacological aspects and bioavailability enhancement approaches. Indian J Pharmacol. 2007;39(4):172.Google Scholar
  14. 14.
    Chen C-H, et al. Synergistic anti-cancer effect of baicalein and silymarin on human hepatoma HepG2 cells. Food Chem Toxicol. 2009;47(3):638–44.Google Scholar
  15. 15.
    Gonzalez-Correa J, et al. Effects of silymarin MZ-80 on hepatic oxidative stress in rats with biliary obstruction. Pharmacology. 2002;64(1):18–27.Google Scholar
  16. 16.
    Anthony KP, Saleh MA. Free radical scavenging and antioxidant activities of silymarin components. Antioxidants. 2013;2(4):398–407.Google Scholar
  17. 17.
    Valenzuela A, Aspillaga M, Vial S, Guerra R. Selectivity of silymarin on the increase of the glutathione content in different tissues of the rat. Planta Med. 1989;55(05):420–2.Google Scholar
  18. 18.
    Valenzuela A, Garrido A. Biochemical bases of the pharmacological action of the flavonoid silymarin and of its structural isomer silibinin. Biol Res. 1994;27:105.PubMedGoogle Scholar
  19. 19.
    Wu J-W, Lin L-C, Tsai T-H. Drug–drug interactions of silymarin on the perspective of pharmacokinetics. J Ethnopharmacol. 2009;121(2):185–93.Google Scholar
  20. 20.
    Cao X, Fu M, Wang L, Liu H, Deng W, Qu R, et al. Oral bioavailability of silymarin formulated as a novel 3-day delivery system based on porous silica nanoparticles. Acta Biomater. 2012;8(6):2104–12.Google Scholar
  21. 21.
    Fu T, Lu J, Guo L, Zhang L, Cai X, Zhu H. Improving bioavailability of silybin by inclusion into SBA-15 mesoporous silica materials. J Nanosci Nanotechnol. 2012;12(5):3997–4006.Google Scholar
  22. 22.
    United States Pharmacopeia and National Formulary (USP 40-NF 35). Rockville, MD: United States Pharmacopeial Convention; 2017, 7112.Google Scholar
  23. 23.
    Yousef MI, Omar SAM, el-Guendi MI, Abdelmegid LA. Potential protective effects of quercetin and curcumin on paracetamol-induced histological changes, oxidative stress, impaired liver and kidney functions and haematotoxicity in rat. Food Chem Toxicol. 2010;48(11):3246–61.Google Scholar
  24. 24.
    Field A. Contrasts and post hoc tests for one-way independent ANOVA using SPSS. C8057 (Research Methods 2). [online]. Available from:[Accessed 3 Nov 2008]; 2000.Google Scholar
  25. 25.
    Cai Q, Luo ZS, Pang WQ, Fan YW, Chen XH, Cui FZ. Dilute solution routes to various controllable morphologies of MCM-41 silica with a basic medium. Chem Mater. 2001;13(2):258–63.Google Scholar
  26. 26.
    Meynen V, Cool P, Vansant EF. Verified syntheses of mesoporous materials. Microporous Mesoporous Mater. 2009;125(3):170–223.Google Scholar
  27. 27.
    Coates J. Interpretation of infrared spectra, a practical approach. In: Meyers RA, editor. Encyclopedia of analytical chemistry. Chichester: John Wiley & Sons Ltd; 2000. p.10815–37.Google Scholar
  28. 28.
    Storck S, Bretinger H, Maier WF. Characterization of micro-and mesoporous solids by physisorption methods and pore-size analysis. Appl Catal A Gen. 1998;174(1–2):137–46.Google Scholar
  29. 29.
    Sayari A, Kruk M, Jaroniec M. Characterization of microporous-mesoporous MCM-41 silicates prepared in the presence of octyltrimethylammonium bromide. Catal Lett. 1997;49(3–4):147–53.Google Scholar
  30. 30.
    Park J, Han Y, Kim H. Formation of mesoporous materials from silica dissolved in various NaOH concentrations: effect of pH and ionic strength. J Nanomater. 2012;2012:74.Google Scholar
  31. 31.
    Thommes M. Physical adsorption characterization of nanoporous materials. Chem Ing Tech. 2010;82(7):1059–73.Google Scholar
  32. 32.
    Appaturi JN, Selvaraj M, Hamid SBA. Synthesis of 3-(2-furylmethylene)-2, 4-pentanedione using DL-alanine functionalized MCM-41 catalyst via Knoevenagel condensation reaction. Microporous Mesoporous Mater. 2018;260:260–9.Google Scholar
  33. 33.
    Singh S, Kanungo M. Alterations in lactate dehydrogenase of the brain, heart, skeletal muscle, and liver of rats of various ages. J Biol Chem. 1968;243(17):4526–9.PubMedGoogle Scholar

Copyright information

© Controlled Release Society 2019

Authors and Affiliations

  1. 1.Department of Pharmaceutics, Faculty of PharmacyAlexandria UniversityAlexandriaEgypt
  2. 2.Department of Pharmaceutics, Faculty of Pharmacy and Drug ManufacturingPharos University in AlexandriaAlexandriaEgypt

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