Skip to main content
SpringerLink
Log in

Encapsulation of plumbagin using cyclodextrins to enhance plumbagin stability: computational simulation, preparation, characterization, and application

  • Original Article
  • Published:
Journal of Inclusion Phenomena and Macrocyclic Chemistry Aims and scope Submit manuscript

Abstract

Encapsulation of plumbagin using cyclodextrins (CDs), including α-cyclodextrin (αCD), β-cyclodextrin (βCD), and γ-cyclodextrin (γCD) to form inclusion complexes was investigated to prevent the loss of plumbagin in pharmaceutical and nutraceutical products. Computational simulations and phase solubility studies suggest that the complex formations of plumbagin with CDs are possible. βCD is chosen, as it has the lowest price and can form the complex in a wide concentration range with 1:1 host–guest molar ratio. Two techniques of the complex formation, co-precipitation and freeze-drying, were evaluated for both pure plumbagin and extracted plumbagin from Plumbago indica root to represent lab-scale and industrial-scale productions, respectively. The complexes from these two techniques can prevent the loss of plumbagin up to three-folds better than plumbagin in free form. The preservation by encapsulation can increase the remaining plumbagin from 22.68 to 60.26% after exposure at 50 °C for 6 weeks.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

References

  1. Padhye, S., Dandawate, P., Yusufi, M., Ahmad, A., Sarkar, F.: Perspectives on medicinal properties of plumbagin and its analogs. Med. Res. Rev. 32, 1131–1158 (2012)

    Article  CAS  PubMed  Google Scholar 

  2. Gangopadhyay, M., Sircar, D., Mitra, A., Bhattacharya, S.: Hairy root culture of Plumbago indica as a potential source for plumbagin. Biol. Plant. 52, 533–537 (2008)

    Article  CAS  Google Scholar 

  3. Rattarom, R., Sakpakdeejaroen, I., Itharat, A.: Cytotoxic effects of the ethanolic extract from Benjakul formula and its compounds on human lung cancer cells. Thai J. Pharmacol. 32, 99–101 (2010)

    Google Scholar 

  4. Kaewbumrung, S., Panichayupakaranant, P.: Antibacterial activity of plumbagin derivative-rich Plumbago indica root extracts and chemical stability. Nat. Prod. Res. 28, 835–837 (2014)

    Article  CAS  PubMed  Google Scholar 

  5. Kuo, P.-L., Hsu, Y.-L., Cho, C.-Y.: Plumbagin induces G2-M arrest and autophagy by inhibiting the AKT/mammalian target of rapamycin pathway in breast cancer cells. Mol. Cancer Ther. 5, 3209–3221 (2006)

    Article  PubMed  Google Scholar 

  6. Checker, R., Sharma, D., Sandur, S.K., Khanam, S., Poduval, T.B.: Anti-inflammatory effects of plumbagin are mediated by inhibition of NF-kappaB activation in lymphocytes. Int. Immunopharmacol. 9, 949–958 (2009)

    Article  CAS  PubMed  Google Scholar 

  7. Tilak, J.C., Adhikari, S., Devasagayam, T.P.: a: Antioxidant properties of Plumbago zeylanica, an Indian medicinal plant and its active ingredient, plumbagin. Redox Rep. 9, 219–227 (2004)

    Article  CAS  PubMed  Google Scholar 

  8. Sharma, I., Gusain, D., Dixit, V.P.: Hypolipidaemic and antiatherosclerotic effects of plumbagin in rabbits. Indian J. Physiol. Pharmacol. 35, 10–14 (1991)

    Article  Google Scholar 

  9. Pinho, E., Grootveld, M., Soares, G., Henriques, M.: Cyclodextrins as encapsulation agents for plant bioactive compounds. Carbohydr. Polym. 101, 121–135 (2014)

    Article  CAS  PubMed  Google Scholar 

  10. Popielec, A., Loftsson, T.: Effects of cyclodextrins on the chemical stability of drugs. Int. J. Pharm. 531, 532–542 (2017)

    Article  CAS  PubMed  Google Scholar 

  11. Szejtli, J.: Introduction and general overview of cyclodextrin chemistry. Chem. Rev. 98, 1743–1754 (1998)

    Article  CAS  PubMed  Google Scholar 

  12. Koontz, J.L., Marcy, J.E., Barbeau, W.E., Duncan, S.E.: Stability of natamycin and its cyclodextrin inclusion complexes in aqueous solution. J. Agric. Food Chem. 51, 7111–7114 (2003)

    Article  CAS  PubMed  Google Scholar 

  13. Bhandari, B.R., D’Arcy, B.R., Padukka, I.: Encapsulation of lemon oil by paste method using β-cyclodextrin: encapsulation efficiency and profile of oil volatiles. J. Agric. Food Chem. 47, 5194–5197 (1999)

    Article  CAS  PubMed  Google Scholar 

  14. Mourtzinos, I., Salta, F., Yannakopoulou, K., Chiou, A., Karathanos, V.T.: Encapsulation of olive leaf extract in β-cyclodextrin. J. Agric. Food Chem. 55, 8088–8094 (2007)

    Article  CAS  PubMed  Google Scholar 

  15. Bothiraja, C., Kapare, H.S., Pawar, A.P., Shaikh, K.S.: Development of plumbagin-loaded phospholipid-Tween® 80 mixed micelles: Formulation, optimization, effect on breast cancer cells and human blood/serum compatibility testing. Ther. Deliv. 4, 1247–1259 (2013)

    Article  CAS  PubMed  Google Scholar 

  16. D’Souza, R., Singh, U.V., Aithal, K.S., Udupa, N.: Antifertility activity of niosomal HPβCD-plumbagin complex. Indian J. Pharm. Sci. 60, 36 (1998)

    Google Scholar 

  17. Singh, U.V., Udupa, N.: Reduced toxicity and enhanced antitumor efficacy of betacyclodextrin plumbagin inclusion complex in mice bearing Ehrlich ascites carcinoma. Indian J. Physiol. Pharmacol. 41, 171–175 (1997)

    CAS  PubMed  Google Scholar 

  18. Oommen, E., Shenoy, B.D., Udupa, N., Kamath, R., Devi, P.U.: Antitumour efficacy of cyclodextrin-complexed and niosome—encapsulated plumbagin in mice bearing melanoma B16F1. Pharm. Pharmacol. Commun. 5, 281–285 (1999)

    Article  CAS  Google Scholar 

  19. Sunil Kumar, M.R., Kiran Aithal, B., Udupa, N., Sreenivasulu Reddy, M., Raakesh, V., Murthy, R.S.R., Prudhvi Raju, D., Rao, S.: B.S.: Formulation of plumbagin loaded long circulating pegylated liposomes: In vivo evaluation in C57BL/6J mice bearing B16F1 melanoma. Drug Deliv. 18, 511–522 (2011)

    Article  CAS  Google Scholar 

  20. Srihakulung, O., Maezono, R., Toochinda, P., Kongprawechnon, W., Intarapanich, A., Lawtrakul, L.: Host-guest interactions of plumbagin with β-cyclodextrin, dimethyl-β-cyclodextrin and hydroxypropyl-β-cyclodextrin: Semi-empirical quantum mechanical PM6 and PM7 methods. Sci. Pharm. 86, 1–11 (2018)

    Article  CAS  Google Scholar 

  21. Astray, G., Gonzalez-Barreiro, C., Mejuto, J.C., Rial-Otero, R., Simal-Gandara, J.: A review on the use of cyclodextrins in foods. Food Hydrocoll. 23, 1631–1640 (2009)

    Article  CAS  Google Scholar 

  22. Cravotto, G., Binello, A., Baranelli, E., Carraro, P., Trotta, F.: Cyclodextrins as food additives and in food processing. Curr. Nutr. Food Sci. 2, 343–350 (2006)

    Article  CAS  Google Scholar 

  23. Jug, M., Beaeireviae-Laaean, M.: Cyclodextrin-based pharmaceuticals. Radiat. Med. Sci. 499, 9–26 (2008)

    Google Scholar 

  24. Del Valle, E.M.M.: Cyclodextrins and their uses: a review. Process Biochem. 39, 1033–1046 (2004)

    Article  CAS  Google Scholar 

  25. Davis, M., Brewster, E.: M.: Cyclodextrin-based pharmaceutics: past, present and future. Nat. Rev. Drug Discov. 3, 1023–1035 (2004)

    Article  CAS  PubMed  Google Scholar 

  26. Buschmann, H.-J., Schollmeyer, E.: Applications of cyclodextrins in cosmetic products: a review. J. Cosmet. Sci. 53, 185–191 (2002)

    CAS  PubMed  Google Scholar 

  27. Viernstein, H., Weiss-Greiler, P., Wolschann, P.: Solubility enhancement of low soluble biologically active compounds by beta-cyclodextrin and dimethyl-beta-cyclodextrin. J. Incl. Phenom. Macrocycl. Chem. 44, 235–239 (2002)

    Article  CAS  Google Scholar 

  28. Savic, I.M., Savic-Gajic, I.M., Nikolic, V.D., Nikolic, L.B., Radovanovic, B.C., Milenkovic-Andjelkovic, A.: Enhencemnet of solubility and photostability of rutin by complexation with β-cyclodextrin and (2-hydroxypropyl)-β-cyclodextrin. J. Incl. Phenom. Macrocycl. Chem. 86, 33–43 (2016)

    Article  CAS  Google Scholar 

  29. Lo Nostro, P., Fratoni, L., Baglioni, P.: Modification of a cellulosic fabric with β-cyclodextrin for textile finishing applications. J. Incl. Phenom. Macrocycl. Chem. 44, 423–427 (2002)

    Article  CAS  Google Scholar 

  30. Layre, A.M., Gosselet, N.M., Renard, E., Sebille, B., Amiel, C.: Comparison of the complexation of cosmetical and pharmaceutical compounds with gamma-cyclodextrin, 2-hydroxypropyl-beta-cyclodextrin and water-soluble beta-cyclodextrin-co-epichlorhydrin polymers. J. Incl. Phenom. Macrocycl. Chem. 43, 311–317 (2002)

    Article  CAS  Google Scholar 

  31. Batt, D.K., Garala, K.C.: Preparation and evaluation of inclusion complexes of diacerein with β-cyclodextrin and hydroxypropyl β-cyclodextrin. J. Incl. Phenom. Macrocycl. Chem. 77, 471–481 (2013)

    Article  CAS  Google Scholar 

  32. Crini, G.: Review: a history of cyclodextrins. Chem. Rev. 114, 10940–10975 (2014)

    Article  CAS  PubMed  Google Scholar 

  33. Li, S.: Cyclodextrins and their applications in analytical chemistry. Chem. Rev. 92, 1457–1470 (1992)

    Article  CAS  Google Scholar 

  34. Hedges, A.R.: Industrial applications of cyclodextrins. Chem. Rev. 98, 2035–2044 (1998)

    Article  CAS  PubMed  Google Scholar 

  35. Allen, F.H.: The Cambridge structural database: a quarter of a million crystal structures and rising. Acta Crystallogr. B. 58, 380–388 (2002)

    Article  CAS  PubMed  Google Scholar 

  36. Vijayalakshmi, J., Rajan, S.S., Srinivasan, R.: Structure of plumbagin. Acta Crystallogr. C43, 2375–2377 (1987)

    CAS  Google Scholar 

  37. Chacko, K.K., Saenger, W.: Topography of cyclodextrin inclusion complexes. 15. Crystal and molecular structure of the cyclohexaamylose-7.57 water complex, form III. Four- and six-membered circular hydrogen bonds. J. Am. Chem. Soc. 103, 1708–1715 (1981)

    Article  CAS  Google Scholar 

  38. Steiner, T., Koellner, G.: Crystalline β-cyclodextrin hydrate at various humidities: fast, continuous, and reversible dehydration studied by X-ray diffraction. J. Am. Chem. Soc. 116, 5122–5128 (1994)

    Article  CAS  Google Scholar 

  39. Harata, K.: The structure of the cyclodextrin complex. XX. Crystal structure of uncomplexed hydrated γ-cyclodextrin. Bull. Chem. Soc. Jpn. 60, 2763–2767 (1987)

    Article  CAS  Google Scholar 

  40. Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., Barone, V., Petersson, G.A., Nakatsuji, H.: Gaussian 16 Revision A. 03. 2016. Gaussian Inc., Wallingford (2016)

    Google Scholar 

  41. Morris, G.M., Huey, R., Lindstrom, W., Sanner, M.F., Belew, R.K., Goodsell, D.S., Olson, A.J.: AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J. Comput. Chem. 30, 2785–2791 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Morris, G.M., Goodsell, D.S., Halliday, R.S., Huey, R., Hart, W.E., Belew, R.K., Olson, A.J.: Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J. Comput. Chem. 19, 1639–1662 (1998)

    Article  CAS  Google Scholar 

  43. Higuchi, T., Connors, K.A.: Phase solubility technique. Adv. Anal. Chem. Instrum. 4, 117–212 (1965)

    CAS  Google Scholar 

  44. Wei, Y., Zhang, J., Zhou, Y., Bei, W., Li, Y., Yuan, Q., Liang, H.: Characterization of glabridin/hydroxypropyl-β-cyclodextrin inclusion complex with robust solubility and enhanced bioactivity. Carbohydr. Polym. 159, 152–160 (2017)

    Article  CAS  PubMed  Google Scholar 

  45. Tommasini, S., Raneri, D., Ficarra, R., Calabrò, M.L., Stancanelli, R., Ficarra, P.: Improvement in solubility and dissolution rate of flavonoids by complexation with β-cyclodextrin. J. Pharm. Biomed. Anal. 35, 379–387 (2004)

    Article  CAS  PubMed  Google Scholar 

  46. Kapadia, N.S., Isarani, S.A., Shah, M.B.: A simple method for isolation of plumbagin from roots of Plumbago rosea. Pharm. Biol. 43, 551–553 (2005)

    Article  CAS  Google Scholar 

  47. Szente, L., Szejtli, J., Kis, G.L.: Spontaneous opalescence of aqueous gamma-cyclodextrin solutions: complex formation or self-aggregation? J. Pharm. Sci. 87, 778–781 (1998)

    Article  CAS  PubMed  Google Scholar 

  48. Sajan, D., Laladhas, K.P., Joe, I.H., Jayakumar, V.S.: Vibrational spectra and density functional theoretical calculations on the antitumor drug, plumbagin. J. Raman Spectrosc. 36, 1001–1011 (2005)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was financial supported by the Tobacco Authority of Thailand and the scholarship for the Excellent Thai Student (ETS) of Sirindhorn International Institute of Technology (SIIT), Thammasat University. The authors gratefully acknowledge the Center of Scientific Equipment for Advanced Research, Thammasat University (TUCSEAR) for providing an access to the analytical instruments.

Author information

Authors and Affiliations

  1. School of Bio-Chemical Engineering and Technology, Sirindhorn International Institute of Technology, Thammasat University, Pathum Thani, 12120, Thailand

    Nathasak Sinlikhitkul, Pisanu Toochinda & Luckhana Lawtrakul

  2. Department of Applied Thai Traditional Medicine, Faculty of Medicine, Thammasat University, Pathum Thani, 12120, Thailand

    Pranporn Kuropakornpong & Arunporn Itharat

Authors
  1. Nathasak Sinlikhitkul
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pisanu Toochinda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luckhana Lawtrakul
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pranporn Kuropakornpong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Arunporn Itharat
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pisanu Toochinda.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sinlikhitkul, N., Toochinda, P., Lawtrakul, L. et al. Encapsulation of plumbagin using cyclodextrins to enhance plumbagin stability: computational simulation, preparation, characterization, and application. J Incl Phenom Macrocycl Chem 93, 229–243 (2019). https://doi.org/10.1007/s10847-018-0870-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10847-018-0870-5

Keywords

Search

Navigation