Skip to main content

Advertisement

SpringerLink
Log in

Brain-Targeted Delivery of Docetaxel by Glutathione-Coated Nanoparticles for Brain Cancer

  • Research Article
  • Theme: Translational Application of Nano Delivery Systems: Emerging Cancer Therapy
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

Gliomas are some of the most aggressive types of cancers but the blood–brain barrier acts as an obstacle to therapeutic intervention in brain-related diseases. The blood–brain barrier blocks the permeation of potentially toxic compounds into neural tissue through the interactions of brain endothelial cells with glial cells (astrocytes and pericytes) which induce the formation of tight junctions in endothelial cells lining the blood capillaries. In the present study, we characterize a glutathione-coated docetaxel-loaded PEG-PLGA nanoparticle, show its in vitro drug release data along with cytotoxicity data in C6 and RG2 cells, and investigate its trans-blood–brain barrier permeation through the establishment of a Transwell cellular co-culture. We show that the docetaxel-loaded nanoparticle’s size enables its trans-blood–brain barrier permeation; the nanoparticle exhibits a steady, sustained release of docetaxel; the drug is able to induce cell death in glioma models; and the glutathione-coated nanoparticle is able to permeate through the Transwell in vitro blood–brain barrier model.

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

Similar content being viewed by others

References

  1. Yared JA, Tkaczuk KH. Update on taxane development: new analogs and new formulations. Drug Des Dev Ther. 2012;6:371.

    CAS  Google Scholar 

  2. Tije AJ, Verweij J, Loos WJ, Sparreboom A. Pharmacological effects of formulation vehicles: implications for cancer chemotherapy. Clin Pharmacokinet. 2003;42(7):665–85.

    Article  PubMed  Google Scholar 

  3. Sanson M, Napolitano M, Yaya R, Keime-Guibert F, Broët P, Hoang-Xuan K, et al. Second line chemotherapy with docetaxel in patients with recurrent malignant glioma: a phase II study. J Neuro-Oncol. 2000;50(3):245–9.

    Article  CAS  Google Scholar 

  4. Kleihues P, Cavenee W. Pathology and genetics of tumours of the nervous system. International Agency for Research on Cancer (IARC) and WHO Health Organisation. Oxford: Oxford Press; 2000.

    Google Scholar 

  5. Lefranc F, Sauvage S, Van Goietsenoven G, Mégalizzi V, Lamoral-Theys D, Debeir O, et al. Narciclasine, a plant growth modulator, activates Rho and stress fibers in glioblastoma cells. Mol Cancer Ther. 2009;8(7):1739–50.

    Article  CAS  PubMed  Google Scholar 

  6. Lefranc F, Brotchi J, Kiss R. Possible future issues in the treatment of glioblastomas: special emphasis on cell migration and the resistance of migrating glioblastoma cells to apoptosis. J Clin Oncol. 2005;23(10):2411–22.

    Article  CAS  PubMed  Google Scholar 

  7. Grobben B, De Deyn P, Slegers H. Rat C6 glioma as experimental model system for the study of glioblastoma growth and invasion. Cell Tissue Res. 2002;310(3):257–70.

    Article  CAS  PubMed  Google Scholar 

  8. Kleihues P, Ohgaki H. Primary and secondary glioblastomas: from concept to clinical diagnosis. Neuro-Oncology. 1999;1(1):44–51.

    CAS  PubMed Central  PubMed  Google Scholar 

  9. Benda P, Lightbody J, Sato G, Levine L, Sweet W. Differentiated rat glial cell strain in tissue culture. Science. 1968;161(3839):370–1.

    Article  CAS  PubMed  Google Scholar 

  10. Geldenhuys W, Mbimba T, Bui T, Harrison K, Sutariya V. Brain-targeted delivery of paclitaxel using glutathione-coated nanoparticles for brain cancers. J Drug Target. 2011;19(9):837–45.

    Article  CAS  PubMed  Google Scholar 

  11. Carroll RT, Bhatia D, Geldenhuys W, Bhatia R, Miladore N, Bishayee A, et al. Brain-targeted delivery of Tempol-loaded nanoparticles for neurological disorders. J Drug Target. 2010;18(9):665–74.

    Article  CAS  PubMed  Google Scholar 

  12. Cecchelli R, Berezowski V, Lundquist S, Culot M, Renftel M, Dehouck M-P, et al. Modelling of the blood–brain barrier in drug discovery and development. Nat Rev Drug Discov. 2007;6(8):650–61.

    Article  CAS  PubMed  Google Scholar 

  13. Meyers JD, Doane T, Burda C, Basilion JP. Nanoparticles for imaging and treating brain cancer. Nanomedicine. 2013;8(1):123–43.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Kuhnline Sloan CD, Nandi P, Linz TH, Aldrich JV, Audus KL, Lunte SM. Analytical and biological methods for probing the blood–brain barrier. Annu Rev Anal Chem. 2012;5:505–31.

    Article  Google Scholar 

  15. Valdovinos-Flores C, Gonsebatt ME. The role of amino acid transporters in GSH synthesis in the blood–brain barrier and central nervous system. Neurochem Int. 2012;61(3):405–14.

    Article  CAS  PubMed  Google Scholar 

  16. Limón-Pacheco JH, Hernández NA, Fanjul-Moles ML, Gonsebatt ME. Glutathione depletion activates mitogen-activated protein kinase (MAPK) pathways that display organ-specific responses and brain protection in mice. Free Radic Biol Med. 2007;43(9):1335–47.

    Article  PubMed  Google Scholar 

  17. Gaillard PJ. Glutathione-based drug delivery system. Google Patents; 2010.

  18. Cecchelli R, Dehouck B, Descamps L, Fenart L, Buée-Scherrer V, Duhem C, et al. In vitro model for evaluating drug transport across the blood–brain barrier. Adv Drug Deliv Rev. 1999;36(2):165–78.

    Article  CAS  PubMed  Google Scholar 

  19. Hatherell K, Couraud P-O, Romero IA, Weksler B, Pilkington GJ. Development of a three-dimensional, all-human<i>in vitro</i>model of the blood–brain barrier using mono-, co-, and tri-cultivation Transwell models. J Neurosci Methods. 2011;199(2):223–9.

    Article  PubMed  Google Scholar 

  20. Gaillard PJ, Voorwinden LH, Nielsen JL, Ivanov A, Atsumi R, Engman H, et al. Establishment and functional characterization of an in vitro model of the blood–brain barrier, comprising a co-culture of brain capillary endothelial cells and astrocytes. Eur J Pharm Sci. 2001;12(3):215–22.

    Article  CAS  PubMed  Google Scholar 

  21. Garcia CM, Darland DC, Massingham LJ, D'Amore PA. Endothelial cell–astrocyte interactions and TGFβ are required for induction of blood–neural barrier properties. Dev Brain Res. 2004;152(1):25–38.

    Article  CAS  Google Scholar 

  22. Sah H, Thoma LA, Desu HR, Sah E, Wood GC. Concepts and practices used to develop functional PLGA-based nanoparticulate systems. Int J Nanomedicine. 2013;8:747.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Danhier F, Ansorena E, Silva JM, Coco R, Le Breton A, Préat V. PLGA-based nanoparticles: an overview of biomedical applications. J Control Release. 2012;161(2):505–22.

    Article  CAS  PubMed  Google Scholar 

  24. Owens III DE, Peppas NA. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm. 2006;307(1):93–102.

    Article  CAS  PubMed  Google Scholar 

  25. Sabzevari A, Adibkia K, Hashemi H, Hedayatfar A, Mohsenzadeh N, Atyabi F, et al. Polymeric triamcinolone acetonide nanoparticles as a new alternative in the treatment of uveitis: In vitro and in vivo studies. Eur J Pharm Biopharm. 2013;84(1):63–71.

    Article  CAS  PubMed  Google Scholar 

  26. Etame AB, Smith CA, Chan WC, Rutka JT. Design and potential application of PEGylated gold nanoparticles with size-dependent permeation through brain microvasculature. Nanomedicine: NBM. 2011;7(6):992–1000.

    Article  CAS  Google Scholar 

  27. Hatakeyama H, Akita H, Maruyama K, Suhara T, Harashima H. Factors governing the in vivo tissue uptake of transferrin-coupled polyethylene glycol liposomes in vivo. Int J Pharm. 2004;281(1):25–33.

    Article  CAS  PubMed  Google Scholar 

  28. Jinwal U, Groshev A, Zhang J, Grover A, Sutariya V. Preparation and Characterization of Methylene blue Nanoparticles for Alzheimer's disease and other Tauopathies. Curr Drug Deliv. 2013.

  29. Wilhelm I, Fazakas C, Krizbai IA. In vitro models of the blood–brain barrier. Acta Neurobiol Exp (Wars). 2011;71(1):113–28.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, 12901 Bruce B. Downs Blvd. MDC 30, Tampa, Florida, 33612-4749, USA

    Aditya Grover, Anjali Hirani, Yashwant Pathak & Vijaykumar Sutariya

Authors
  1. Aditya Grover
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anjali Hirani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yashwant Pathak
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vijaykumar Sutariya
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vijaykumar Sutariya.

Additional information

Guest Editors: Mahavir B. Chougule and Chalet Tan

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Grover, A., Hirani, A., Pathak, Y. et al. Brain-Targeted Delivery of Docetaxel by Glutathione-Coated Nanoparticles for Brain Cancer. AAPS PharmSciTech 15, 1562–1568 (2014). https://doi.org/10.1208/s12249-014-0165-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-014-0165-0

KEY WORDS

Search

Navigation