AAPS PharmSciTech

, Volume 15, Issue 4, pp 1000–1008 | Cite as

Nanoemulsion for Solubilization, Stabilization, and In Vitro Release of Pterostilbene for Oral Delivery

  • Yue Zhang
  • Zhenhua Shang
  • Chunhui Gao
  • Man Du
  • Shixia Xu
  • Haiwen Song
  • Tingting Liu
Research Article


Pterostilbene, being extracted from many plants, has significant biological activities in preventing cancer, diabetes, and cardiovascular diseases so as to have great potential applications in pharmaceutical fields. But the poor solubility and stability of pterostilbene strictly restrained its applications. As a good protection and oral delivery system, an optimal nanoemulsion for pterostilbene was developed by using low-energy emulsification method. Systematic pseudo-ternary phase diagrams have been studied in optimization of nanoemulsion formulations. The prepared pterostilbene nanoemulsion was characterized by transmission electron microscope, Fourier transform Raman spectrum, and laser droplet size analyzer. Nanoemulsion droplets are circular with smooth margin, and the mean size is 55.8 ± 10.5 nm. The results illustrated that the nanoemulsion as oral delivery system dramatically improved the stability and solubility of pterostilbene, and in vitro release of pterostilbene was significantly improved (96.5% in pH 3.6 buffer; 13.2% in pH 7.4 buffer) in comparison to the pterostilbene suspension (lower than 21.4% in pH 3.6 buffer; 2.6% in pH 7.4 buffer).


3,5-dimethoxyl-4′-hydroxystilbene nanoemulsion pseudo-ternary phase diagram pterostilbene release study 



We express our gratitude for the team fund of Hebei University of Science and Technology (XL201114, QD201211), Hebei Medical and Chemical Engineering Centre, and Pharmaceutical Molecular Chemistry Key Laboratory of Ministry Technology.


  1. 1.
    Jeandet P, Breuil A, Adrian M, Weston L, Debord S, Meunier P, et al. HPLC analysis of grapevine phytoalexins coupling photodiode array detection and fluorometry. Anal Chem. 1997;69:5172–5.CrossRefGoogle Scholar
  2. 2.
    Spath E, Schlager J. Constituents of red sandalwood. II. Constitution of pterostilbene. Berichte der Deutschen Chemischen Gesellschaft [Abteilung] B: Abhandlungen. 1940;73B:881–4Google Scholar
  3. 3.
    Seshadri TR. Polyphenols of Pterocarpus and Dalbergia woods. Phytochemistry. 1972;11:881–98.CrossRefGoogle Scholar
  4. 4.
    Ghisalberti EL, Jefferies PR, Lanteri R, Matisons J. Constituents of propolis. Experientia. 1978;34:157–8.CrossRefGoogle Scholar
  5. 5.
    Langcake P, Cornford C, Pryce R. Identification of pterostilbene as a phytoalexin from Vitis vinifera leaves. Phytochemistry. 1979;18:1025–7.CrossRefGoogle Scholar
  6. 6.
    Mathew J, Rao A. Chemical examination of Pterocarpus marsupium. J Indian Chem Soc. 1984;61:728–9.Google Scholar
  7. 7.
    Rimando A, Cody R. Determination of stilbenes in blueberries. LCGC North America. 2005;23:1192, 1194, 1196, 1198, 1200.Google Scholar
  8. 8.
    Adrian M, Jeandet P, Douiller-Breuil A, Tesson L, Bessis R. Stilbene content of mature Vitis vinifera berries in response to UV-C elicitation. J Agric Food Chem. 2000;48:6103–5.PubMedCrossRefGoogle Scholar
  9. 9.
    Wang X, Lu W, Chen J, Lu Y, Wu N, Kang W, et al. Studies on the chemical constituents of chloroform extract of Dracaena cochinchinensis. Yaoxue Xuebao. 1998;33(10):755–8.Google Scholar
  10. 10.
    King FE, King TJ, Manning LC. The Gibbs reaction and the constitution of jacareubin. J Chem Soc. 1957;51:563–6.Google Scholar
  11. 11.
    Paul B, Masih I, Deopujari J, Charpentier C. Occurrence of resveratrol and pterostilbene in age-old darakchasava, an Ayurvedic medicine from India. J Ethnopharmacol. 1999;68:71–6.PubMedCrossRefGoogle Scholar
  12. 12.
    Perecko T, Drabikova K, Rackova L, Ciz M, Podborska M, Lojek A, et al. Molecular targets of the natural antioxidant pterostilbene: effect on protein kinase C, caspase-3 and apoptosis in human neutrophils in vitro. Neuroendocrinol Lett. 2010;31:84–90.PubMedGoogle Scholar
  13. 13.
    Chiou Y, Tsai M, Nagabhushanam K, Wang YJ, Wu CH, Ho CT, et al. Pterostilbene is more potent than resveratrol in preventing azoxymethane (AOM)-induced colon tumorigenesis via activation of the NF-E2-related factor 2 (Nrf2)-mediated antioxidant signaling pathway. J Agric Food Chem. 2011;59:2725–33.PubMedCrossRefGoogle Scholar
  14. 14.
    Hougee S, Faber J, Sanders A, De J, Romy B, Wim B, et al. Selective COX-2 inhibition by a Pterocarpus marsupium extract characterized by pterostilbene, and its activity in healthy human volunteers. Planta Med. 2005;71:387–92.PubMedCrossRefGoogle Scholar
  15. 15.
    Pan M, Chang Y, Badmaev V, Nagabhushanam K, Ho C. Pterostilbene induces apoptosis and cell cycle arrest in human gastric carcinomal cells. Food Chem. 2007;55:7777–83.CrossRefGoogle Scholar
  16. 16.
    Ferrer P, Asensi M, Ramon S, Ortega A, Benlloch M, Obrador E, et al. Association between pterostilbene and quercetin inhibits metastatic activity of B16 melanoma. Neoplasia. 2005;7:37–47.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Tolomeo M, Grimaudo S, Cristina A, Roberti M, Pizzirani D, Meli M, et al. Pterostilbene and 3′-hydroxypterostilbene are effective apoptosis-inducing agents in MDR and BCR-ABL-expressing leukemia cells. Int J Biochem Cell Biol. 2005;37:1709–12.PubMedCrossRefGoogle Scholar
  18. 18.
    Schneider J, Alosi J, McDonald D, McFadden D. Pterostilbene inhibits lung cancer through induction of apoptosis. J Surg Res. 2010;161:18–22.PubMedCrossRefGoogle Scholar
  19. 19.
    Lee M, Pan M, Chiou Y, Cheng A, Huang H. Resveratrol modulates MED28 (magicin/EG1) expression and inhibits epidermal growth factor (EGF)-induced migration in MDA-MB-231. human breast cancer cells. J Agric Food Chem. 2011; Online Computer File.Google Scholar
  20. 20.
    Gutiérrez J, González C, Maestro A, Sole I, Pey C, Nolla J. Nano-emulsions: new applications and optimization of their preparation. Curr Opin Colloid Interface Sci. 2008;13:245–51.CrossRefGoogle Scholar
  21. 21.
    Liu Y, Zhang D, Zou D, Wang Y, Duan C, Jia L, et al. Transmission of visible and ultraviolet light through charge-stabilized nanoemulsions. J Biomed Nanotechnol. 2011;7:621–31.PubMedCrossRefGoogle Scholar
  22. 22.
    Szebeni J, Alving C, Savay S. Formation of complement-activating particles in aqueous solutions of Taxol: possible role in hypersensitivity reactions. Int J Immunopharmacol. 2001;1(4):721–35.CrossRefGoogle Scholar
  23. 23.
    Gong Y, Wu Y, Zheng C, Fan L, Xiong F, Zhu J. An excellent delivery system for improving the oral bioavailability of natural vitamin E in rats. AAPS Pharm Sci Technol. 2012;13(3):961–6.CrossRefGoogle Scholar
  24. 24.
    Chang L, Wu C, Liu C, Chuo W, Li P, Tsai T. Preparation, characterization and cytotoxicity evaluation of tanshinone IIA nanoemulsions. J Biomed Nanotechnol. 2011;7:558–67.PubMedCrossRefGoogle Scholar
  25. 25.
    Desai NS, Nagarsenker MS. Design and evaluation of self-nanoemulsifying pellets of repaglinide. AAPS Pharm Sci Technol. 2013;14(3):994–1003.CrossRefGoogle Scholar
  26. 26.
    Vandamme T, Anton N. Low-energy nanoemulsification to design veterinary controlled drug delivery devices. Int J Nanomedicine. 2010;5:867–73.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Wang L, Dong J, Chen J, Eastoe J, Li X. Design and optimization of a new self-nanoemulsifying drug delivery system. J Colloid Interface Sci. 2009;330:443–8.PubMedCrossRefGoogle Scholar
  28. 28.
    Elnaggar Y, El-Massik M, Abdallah O. Sildenafil citrate nanoemulsion vs. self-nanoemulsifying delivery systems: rational development and transdermal permeation. Int J Nanotechnol. 2011;8(8/9):749–63.CrossRefGoogle Scholar
  29. 29.
    Uso’n N, Garcia M, Solans C. Formation of water-in-oil (W/O) nano-emulsions in a water/mixed non-ionic surfactant/oil systems prepared by a low-energy emulsification method. Colloids Surf A Physicochem Eng Asp. 2004;250(1–3):415–21.CrossRefGoogle Scholar
  30. 30.
    Porras M, Solans C, González C, Martinez A, Guinart A, Gutierrez J. Studies of formation of W/O nano-emulsions. Colloids Surf A Physicochem Eng Asp. 2004;249:115–8.CrossRefGoogle Scholar
  31. 31.
    Wang L, Li X, Zhang G, Dong J, Eastoe J. Oil-in-water nanoemulsions for pesticide formulations. J Colloid Interface Sci. 2007;314:230–5.PubMedCrossRefGoogle Scholar
  32. 32.
    Zhang Y, Zhao SC. Process for preparation of stilbene compounds by Kornblum oxidation, C.N.; 2010. Patent 101,838,173 Sep 22.Google Scholar
  33. 33.
    Bali V, Ali M, Ali J. Study of surfactant combinations and development of a novel nanoemulsion for minimizing variations in bioavailability of ezetimibe. Colloids Surf B: Biointerfaces. 2010;76:410–20.PubMedCrossRefGoogle Scholar
  34. 34.
    Liu G, Zhang J, Wu P, Li J, Liu Y, Zhou X, et al. Preparation and evaluation of O/W pharmaceutical microemulsions. Zhongguo Nongye Kexue (Beijing, China). 2009;42(9):3328–33.Google Scholar
  35. 35.
    Chinese State Food and Drug Administration. Chinese Pharmacopoeia, 2010 ed. Appendix XIX c, Material medicine and pharmaceutical preparations stability experiment principle; Appendix V C, HPLC method; 2010.Google Scholar
  36. 36.
    Pan G, Jia X, Wei H. Comparison among several preparation methods for pseudo-ternary phase diagrams of pharmaceutical microemulsions. J Chin Pharm. 2006;17:21–3.Google Scholar
  37. 37.
    Sagitani H. Making homogeneous and fine droplet O/W emulsions using nonionic surfactants. J Am Oil Chem Soc. 1981;58:738–43.CrossRefGoogle Scholar
  38. 38.
    Dai L, Li W, Hou X. Effect of the molecular structure of mixed nonionic surfactants on the temperature of miniemulsion formation. Colloids Surf A Physicochem Eng Asp. 1997;125:27–32.CrossRefGoogle Scholar
  39. 39.
    Warisnoicharoen W, Lansley AB, Lawrence MJ. Nonionic oil-in-water microemulsions: the effect of oil type on phase behavior. Int J Pharm. 2000;198:7–27.PubMedCrossRefGoogle Scholar
  40. 40.
    Lamaallam S, Bataller H, Dicharry C, Lachaise J. Formation and stability of miniemulsions produced by dispersion of water/oil/surfactants concentrates in a large amount of water. Colloids Surf A Physicochem Eng Asp. 2005;270–271:44–51.CrossRefGoogle Scholar
  41. 41.
    Pons R, Carrera I, Caelles J, Rouch J, Panizza P. Formation and properties of miniemulsions formed by microemulsions dilution. Adv Colloid Interf Sci. 2003;106:129–46.CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2014

Authors and Affiliations

  • Yue Zhang
    • 1
    • 2
    • 3
  • Zhenhua Shang
    • 1
    • 2
    • 3
  • Chunhui Gao
    • 4
  • Man Du
    • 1
  • Shixia Xu
    • 1
  • Haiwen Song
    • 1
  • Tingting Liu
    • 1
  1. 1.School of Chemical and Pharmaceutical EngineeringHebei University of Science and TechnologyShijiazhuangChina
  2. 2.Hebei Research Center of Pharmaceutical and Chemical EngineeringShijiazhuangChina
  3. 3.State Key Laboratory Breeding Base-Hebei Province Key Laboratory of Molecular Chemistry for DrugsShijiazhuangChina
  4. 4.Zizhu PharmaceuticalQinhuangdaoChina

Personalised recommendations