Nothing Special   »   [go: up one dir, main page]
Skip to main content

Advertisement

Springer Nature Link
Log in

Chitosan-Raloxifene nanoparticle containing doxorubicin as a new double-effect targeting vehicle for breast cancer therapy

  • Research article
  • Published:
DARU Journal of Pharmaceutical Sciences Aims and scope Submit manuscript

Abstract

Background

treatment of breast cancer as one of the most common cancers in the world remains an important area of drug development based on nanoparticulate systems. Effective targeted therapy of affected cells based on ligand conjugate biocompatible polymeric nanoparticles is an attractive perspective in this context.

Objective

In this study, a novel double effect nanoparticle based on Chitosan-Raloxifene conjugate was prepared for adjuvant therapy (hormone and chemo therapy) and drug targeting to breast cancer cells via estrogen receptor (ER).

Methods

Chitosan-raloxifene conjugate was synthesized. Related nanoparticles containing doxorubicin (DOX) were prepared and characterized. Experimental design study was performed to determine the optimum levels of variables in the preparation of nanoparticle. Drug loading, release, nanoparticle stability, and the effect of nanoparticles on cell viability were evaluated. Further, inhibition tests were performed to demonstrate that the function of these novel nanoparticles is mediated via ER.

Results

Chitosan-raloxifene conjugate was successfully synthesized. The prepared nanoparticles showed sizes within 25–35 nm, more than 95% drug loading, about 60% of drug release and desired stability after 24 h. XTT assay on MCF-7 cell line illustrated that these nanoparticles could inhibit the cellular growth up to 60%. The results from inhibition tests revealed that prepared nanoparticles can inhibit cell growth via ER blocking.

Conclusion

This study introduced chitosan-raloxifene nanoparticles containing doxorubicin as a novel targeting agent for adjuvant therapy of breast cancer.

Graphical abstract

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Similar content being viewed by others

References

  1. Chidambaram M, Manavalan R, Kathiresan K. Nanotherapeutics to overcome conventional cancer chemotherapy limitations. J Pharm Pharm Sci. 2011;14(1):67–77.

    Article  Google Scholar 

  2. Yousefpour P, Atyabi F, Vasheghani-Farahani E, Movahedi A-AM, Dinarvand R. Targeted delivery of doxorubicin-utilizing chitosan nanoparticles surface-functionalized with anti-Her2 trastuzumab. Int J Nanomedicine. 2011;6:1977.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Islam MS, Haque P, Rashid TU, Khan MN, Mallik AK, Khan MNI, et al. Core–shell drug carrier from folate conjugated chitosan obtained from prawn shell for targeted doxorubicin delivery. J Mater Sci Mater Med. 2017;28(4):55.

    Article  Google Scholar 

  4. Naruphontjirakul P, Viravaidya-Pasuwat K, Editors. Development of doxorubicin—Core Shell chitosan nanoparticles to treat Cancer. Proceedings of the international conference on biomedical engineering and technology; IACSIT Press: Singapore; 2011.

  5. Bernkop-Schnürch A, Dünnhaupt S. Chitosan-based drug delivery systems. Eur J Pharm Biopharm. 2012;81(3):463–9.

    Article  Google Scholar 

  6. Samadi FY, Mohammadi Z, Yousefi M, Majdejabbari S. Synthesis of raloxifene–chitosan conjugate: a novel chitosan derivative as a potential targeting vehicle. Int J Biol Macromol. 2016;82:599–606.

    Article  CAS  Google Scholar 

  7. Qi L-F, Xu Z-R, Li Y, Jiang X, Han X-Y. In vitro effects of chitosan nanoparticles on proliferation of human gastric carcinoma cell line MGC803 cells. World J Gastroenterol: WJG. 2005;11(33):5136–41.

    CAS  PubMed  Google Scholar 

  8. Jing H, Guo Z, Guo W, Yang W, Xu P, Zhang X. Synthesis and characterization of folic acid modified water-soluble chitosan derivatives for folate-receptor-mediated targeting. Bioorg Med Chem Lett. 2012;22(10):3418–24.

    Article  CAS  Google Scholar 

  9. Mourya V, Inamdar NN. Chitosan-modifications and applications: opportunities galore. React Funct Polym. 2008;68(6):1013–51.

    Article  CAS  Google Scholar 

  10. Mohammadi Z, Abolhassani M, Dorkoosh F, Hosseinkhani S, Gilani K, Amini T, et al. Preparation and evaluation of chitosan–DNA–FAP-B nanoparticles as a novel non-viral vector for gene delivery to the lung epithelial cells. Int J Pharm. 2011;409(1):307–13.

    Article  CAS  Google Scholar 

  11. Gil EMC. Targeting the PI3K/AKT/mTOR pathway in estrogen receptor-positive breast cancer. Cancer Treat Rev. 2014;40(7):862–71.

    Article  Google Scholar 

  12. Pritchard K. Endocrine therapy: is the first generation of targeted drugs the last? J Intern Med. 2013;274(2):144–52.

    Article  CAS  Google Scholar 

  13. Wood AJ, Riggs BL, Hartmann LC. Selective estrogen-receptor modulators—mechanisms of action and application to clinical practice. N Engl J Med. 2003;348(7):618–29.

    Article  Google Scholar 

  14. Fan P, Jordan VC. Acquired resistance to selective estrogen receptor modulators (SERMs) in clinical practice (tamoxifen & raloxifene) by selection pressure in breast cancer cell populations. Steroids. 2014;90:44–52.

    Article  CAS  Google Scholar 

  15. Goldstein SR, Siddhanti S, Ciaccia AV, Plouffe L. A pharmacological review of selective oestrogen receptor modulators. Hum Reprod Update. 2000;6(3):212–24.

    Article  CAS  Google Scholar 

  16. Muchmore DB. Raloxifene: a selective estrogen receptor modulator (SERM) with multiple target system effects. Oncologist. 2000;5(5):388–92.

    Article  CAS  Google Scholar 

  17. Dutertre M, Smith CL. Molecular mechanisms of selective estrogen receptor modulator (SERM) action. J Pharmacol Exp Ther. 2000;295(2):431–7.

    CAS  PubMed  Google Scholar 

  18. Abdel-Hafez SM, Hathout RM, Sammour OA. Towards better modeling of chitosan nanoparticles production: screening different factors and comparing two experimental designs. Int J Biol Macromol. 2014;64:334–40.

    Article  CAS  Google Scholar 

  19. Motwani SK, Chopra S, Talegaonkar S, Kohli K, Ahmad FJ, Khar RK. Chitosan–sodium alginate nanoparticles as submicroscopic reservoirs for ocular delivery: formulation, optimisation and in vitro characterisation. Eur J Pharm Biopharm. 2008;68(3):513–25.

    CAS  PubMed  Google Scholar 

  20. Gazori T, Khoshayand MR, Azizi E, Yazdizade P, Nomani A, Haririan I. Evaluation of alginate/chitosan nanoparticles as antisense delivery vector: formulation, optimization and in vitro characterization. Carbohydr Polym. 2009;77(3):599–606.

    Article  CAS  Google Scholar 

  21. Janes KA, Fresneau MP, Marazuela A, Fabra A. Alonso MaJ. Chitosan nanoparticles as delivery systems for doxorubicin. J Control Release. 2001;73(2):255–67.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge Iran National Science Foundation (INSF) for financial support (grant number 91004795), and Mrs. Saadat for her valuable assistance.

Author information

Author notes

  1. Zohreh Mohammadi and Fatemeh Yazdi Samadi contributed equally to this work.

Authors and Affiliations

  1. School of Pharmacy-International Campus, Iran University of Medical Sciences, Tehran, Iran

    Zohreh Mohammadi

  2. Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran

    Fatemeh Yazdi Samadi

  3. Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Soheila Rahmani

  4. Department of Biology, Science and Research branch, Islamic Azad University, Tehran, Iran

    Zeynab Mohammadi

Authors
  1. Zohreh Mohammadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fatemeh Yazdi Samadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Soheila Rahmani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zeynab Mohammadi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zohreh Mohammadi.

Ethics declarations

Conflict of interest

None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of the paper.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 16 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mohammadi, Z., Samadi, F.Y., Rahmani, S. et al. Chitosan-Raloxifene nanoparticle containing doxorubicin as a new double-effect targeting vehicle for breast cancer therapy. DARU J Pharm Sci 28, 433–442 (2020). https://doi.org/10.1007/s40199-020-00338-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40199-020-00338-9

Keywords

Search

Navigation