Skip to main content

Advertisement

SpringerLink
Log in

Antitumoral and MMP-2 inhibition activity of raloxifene or tamoxifen loaded nanoparticles containing dimethyl-β-cyclodextrin

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

Abstract

A new nanoparticle formulation has been developed by using dimethyl-β-cyclodextrin (DM-β-CD) with raloxifene HCl or tamoxifene citrate. Both drugs are insoluble in water and represent as low bioavailibilities when given orally. Tamoxifen has an FDA approval for breast cancer prevention and the treatment. Raloxifene is approved for osteoprosis treatment. Both drugs were selected as a model drug antitumoural activity and MMP-2 inhibition studies were evaluated on breast cancer cell lines MCF-7 and MDA-MB 231. MMP-2 is known to be responsible for tumour invasion and initation the of angiogenesis. DM-β-CD and sodium taurocholate (NaTC) have been used as absorption enhancers to increase penetration effect of raloxifene/tamoxifen on the tumour cells and aimed to provide high antitumoral activity and MMP-2 inhibition results by developed nanoparticle formulations. The effects of two absorption enhancers were compared. The highest antitumoral activity was observed for DM-β-CD—raloxifene HCl nanoparticle formulation and also MMP-2 enzyme inhibit effectively.

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

Similar content being viewed by others

References

  1. Rasheed, A., Ashok Kumar, C.K., Sravanthi, V.V.N.S.S.: Cyclodextrins as drug carrier molecule: a review. Sci. Pharm. 76, 567–598 (2008)

    Article  CAS  Google Scholar 

  2. Uekama, K., Hirayama, F., Irie, T.: Cyclodextrin drug carrier systems. Chem. Rev. 98, 2045–2076 (1998)

    Article  CAS  Google Scholar 

  3. Challa, R., Ahuja, A., Ali, J., Khar, R.K.: Cyclodextrins in drug delivery: an updated review. AAPS PharmSciTech. 6(2), E329–E357 (2005)

    Article  Google Scholar 

  4. Fontanges, E., Fontana, A., Delmas, P.: Osteoporosis and breast cancer. Joint Bone Spine 71, 102–110 (2004)

    Article  Google Scholar 

  5. Hortobagyi, G.N.: The curability of breast cancer: present and future. EJC Suppl. 1(1), 24–34 (2003)

    Article  Google Scholar 

  6. Kristensen, V.N., Børresen-Dale, A.L.: Molecular epidemiology of breast cancer: genetic variation in steroid hormone metabolism. Mutat. Res. 462, 323–333 (2000)

    Article  CAS  Google Scholar 

  7. Cheong, I., Huang, X., Bettegowda, C., Diaz, L.A.J., Kinzler, K.W., Zhou, S.B.: A bacterial protein enhances the release and efficacy of liposomal cancer drugs. Science 314, 308–311 (2006)

    Article  Google Scholar 

  8. Moghimi, S.M., Hunter, A.C., Murray, J.C.: Nanomedicine: current status and future prospects. FASEB J. 19(3), 11–30 (2005)

    Article  Google Scholar 

  9. Guan, M., Zhou, Y., Zhu, Q.L., Liu, Y., Bei, Y.Y., Zhang, X.N., Zhang, Q.: N-trimethyl chitosan nanoparticle-encapsulated lactosyl-norcantharidin for liver cancer therapy with high targeting efficacy. Nanomedicine 8, 1172–1181 (2012)

    Article  CAS  Google Scholar 

  10. Haley, B., Frenkel, E.: Nanoparticles for drug delivery in cancer treatment. Urol. Oncol. 26, 57–64 (2008)

    Article  CAS  Google Scholar 

  11. Zhu, L., Kate, P., Torchilin, V.P.: Matrix metalloprotease 2-responsive multifunctional liposomal nanocarrier for enhanced tumor targeting. ACS Nano 4(6), 3491–3498 (2012)

    Article  Google Scholar 

  12. Pellikainen, J.M., Kirsi, M., Ropponen, K.M., Kataja, V.V., Kellokoski, J.K., Eskelinen, M.J., Kosma, V.M.: Expression of matrix metalloproteinase (MMP)-2 and MMP-9 in breast cancer with a special reference to activator protein-2, her2, and prognosis. Clin. Cancer Res. 1, 7621–7628 (2004)

    Article  Google Scholar 

  13. La Rocca, G., Pucci-Minafra, I., Marrazzo, A., Taormina, P., Minafra, S.: Zymographic detection and clinical correlations of MMP-2 and MMP-9 in breast cancer sera. Br. J. Cancer 90, 1414–1421 (2004)

    Article  Google Scholar 

  14. Liu, Z., Jiao, Y., Wang, Y., Zhou, C., Zhang, Z.: Polysaccharides-based nanoparticles as drug delivery systems. Adv. Drug Deliv. Rev. 60, 1650–1662 (2008)

    Article  CAS  Google Scholar 

  15. Hassani, L.N.: Hendra F, Bouchemal K: Auto-associative amphiphilic polysaccharide. Drug Discov. Today 17, 608–614 (2012)

    Article  CAS  Google Scholar 

  16. Bernkop-Schnürch, A., Dünnhaupt, S.: Chitosan-based drug delivery systems. Eur. J. Pharm. Biopharm. 81, 463–469 (2012)

    Article  Google Scholar 

  17. Qi, L., Xu, Z., Jiang, X., Hu, C., Xiangfei, Z.: Preparation and antibacterial activity of chitosan nanoparticles. Carbohydr. Res. 339, 2693–2700 (2004)

    Article  CAS  Google Scholar 

  18. Trontelj, J., Vovk, T., Bogataj, M., Mrhar, A.: HPLC analysis of raloxifene hydrochloride and its application to drug quality control studies. Pharmacol. Res. 52, 334–339 (2005)

    Article  CAS  Google Scholar 

  19. Fontana, G., Maniscalco, L., Schillaci, D., Cavallaro, G., Giammona, G.: Solid lipid nanoparticles containing tamoxifen characterization and ın vitro antitumoral activity. Drug Deliv. 12, 385–392 (2005)

    Article  CAS  Google Scholar 

  20. Değim, Z., Ünal, N., Eşsiz, D., Abbasoğlu, U.: Caco-2 cell culture as a model for famotidine absorption. Drug Deliv. 12, 27–33 (2005)

    Google Scholar 

  21. El-Gazayerly, O.N., Hikal, A.H.: Preparation and evaluation of acetazolamide liposomes as an ocular delivery system. Int. J. Pharm. 158, 121–127 (1997)

    Article  CAS  Google Scholar 

  22. Li, H., Song, J.H., Park, J.S., Han, K.: Polyethylene glycol-coated liposomes for oral delivery of recombinant human epidermal growth factor. Int. J. Pharm. 258, 11–19 (2003)

    Article  CAS  Google Scholar 

  23. Mutlu, N.B., Değim, Z., Yılmaz, Ş., Eşsiz, D., Nacar, A.: New perspective for the treatment of alzheimer diseases: liposomal rivastigmine formulations. Drug Dev. Ind. Pharm. 37(7), 775–789 (2011)

    Article  CAS  Google Scholar 

  24. Rouf, M.A., Vural, İ., Renoir, J.M., Hıncal, A.A.: Development and characterization of liposomal formulations for rapamycin delivery and investigation of their antiproliferative effect on MCF7 cells. J. Lipid Res. 19(4), 322–331 (2009)

    CAS  Google Scholar 

  25. Liko, F., Erdoğan, S., Özer, Y.A., Vural, I.: In vitro studies on 5-florouracil-loaded DTPA-PE containing nanosized pegylated liposomes for diagnosis and treatment of tumor. J. Lipid Res. 23(1), 61–69 (2013)

    CAS  Google Scholar 

  26. Van der Merwe, S.M., Verhoef, J.C., Kotzé, A.F., Junginger, H.E.: N-trimethyl chitosan chloride (TMC) as absorption enhancer in oral peptide drug delivery. Development and characterization of minitablet and granule formulations. Eur. J. Pharm. Biopharm. 57, 85–91 (2004)

    Article  Google Scholar 

  27. Degim, Z., Degim, T., Acarturk, F., Erdoğan, D., Özoğul, C., Köksal, M.: Rectal and vaginal administration of insulin-chitosan formulations: an experimental study in rabbits. J. Drug Target 13(10), 563–572 (2005)

    Article  CAS  Google Scholar 

  28. Hsieh, C.Y., Santell, R.C., Haslam, S.Z., Helferich, W.G.: Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo. Cancer Res. 58, 3833–3838 (1998)

    CAS  Google Scholar 

  29. Bartucci, M., Morelli, C., Mauro, L., Ando, S., Surmacz, E.: Differential insulin-like growth factor I receptor signaling and function in estrogen receptor (er)-positive MCF-7 and er-negative MDA-MB-231 breast cancer cells. Cancer Res. 61, 6747–6754 (2001)

    CAS  Google Scholar 

  30. Goldstein, S.R., Siddhanti, S., Ciaccia, A.V., Plouffe, L.: A pharmacological review of selective ostrogen receptor modulators. Hum. Reprod. Update 6(3), 212–224 (2000)

    Article  CAS  Google Scholar 

  31. McDonnell, D.P.: The molecular pharmacology of estrogen receptor modulators: implications for the treatment of breast cancer. Clin. Cancer Res. 11(2 Pt 2), 871s–877s (2005)

    CAS  Google Scholar 

  32. Halvorsen, B., Staff, A.C., Ligaarden, S., Prydz, K., Kolset, S.O.: Lithocholic acid and sulphated lithocholic acid differ in the ability to promote matrix metalloproteinase secretion in the human colon cancer cell line Caco-2. Biochem. J. 349, 189–193 (2000)

    Article  CAS  Google Scholar 

  33. Yücel, Ç., Degim, Z., Yılmaz, Ş.: Nanoparticle and liposome formulations of doxycycline: transport properties through Caco-2 cell line and effects on matrix metalloproteinase secretion. Biomed. Pharmacother. 67, 459–467 (2013)

    Article  Google Scholar 

Download references

Acknowledgments

This study was supported by a research grant from TÜBİTAK Project Number: 109S221, Gazi University (02/2010-39) and Novartis Pharmaceutical Company Research project awards, Turkey.

Conflict of interest

Authors declare here that this paper is original paper and there is no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Technology, Faculty of Pharmacy, Gazi University, 06330, Ankara, Turkey

    N. B. Mutlu Ağardan & Z. Değim

  2. Food and Mouth Diseases Institute, 06520, Ankara, Turkey

    Ş. Yilmaz

Authors
  1. N. B. Mutlu Ağardan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Z. Değim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ş. Yilmaz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Z. Değim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mutlu Ağardan, N.B., Değim, Z. & Yilmaz, Ş. Antitumoral and MMP-2 inhibition activity of raloxifene or tamoxifen loaded nanoparticles containing dimethyl-β-cyclodextrin. J Incl Phenom Macrocycl Chem 80, 31–36 (2014). https://doi.org/10.1007/s10847-014-0395-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10847-014-0395-5

Keywords

Search

Navigation