Tumor Biology

, Volume 35, Issue 5, pp 4799–4806 | Cite as

Efficacy of Cisplatin-loaded polybutyl cyanoacrylate nanoparticles on the glioblastoma

  • Hasan Ebrahimi Shahmabadi
  • Fatemeh Movahedi
  • Maedeh Koohi Moftakhari Esfahani
  • Seyed Ebrahim Alavi
  • Ali Eslamifar
  • Gholamreza Mohammadi Anaraki
  • Azim Akbarzadeh
Research Article


Glioblastoma is known as one of the most aggressive human cancers. To gain access of the brain, therapeutic agents must overcome blood–brain barrier (BBB). In this study, Cisplatin (Cispt)-loaded polybutylcyanoacrylate (PBCA) nanoparticles (NPs) were prepared through miniemulsion polymerization technique. They were coated with polysorbate 80 to cross the BBB of glioblastoma-bearing rats. Prepared NPs were characterized with respect to their size, size distribution, zeta potential, drug loading and encapsulation efficiency, cytotoxicity effects, drug release, and stability pattern. Size and zeta potential of nanodrug were found to be 489 nm and −20 mV, while drug loading and encapsulation efficiency were determined to be 5 % and 25 %, respectively. Release studies demonstrated high retention capability of nanodrug in that 3.18 % of Cispt was released from NPs in a period of 51 h. NPs presented acceptable stability after 2 months and lyophilization. Mean survival time in nanodrug receivers was 19.6 days, while it was 17.5 days for free drug receivers. Histological studies demonstrated efficacy of PBCA NPs in reducing side effects. Finally, such preparation can be considered as a promising nanocarrier for other types of tumor.


Cisplatin PBCA NPs Brain tumor In vivo study Drug delivery 


  1. 1.
    Beduneau A, Saulnier P, Benoit J. Active targeting of brain tumors using nanocarriers. Biomaterials. 2007;28:4947–67.CrossRefPubMedGoogle Scholar
  2. 2.
    Tian XH, Lin XN, Wei F, Feng W, Huang ZC, Wang P, et al. Enhanced brain targeting of temozolomide in polysorbate-80 coated polybutylcyanoacrylate nanoparticles. Int J Nanomedicine. 2011;6:445–52.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Chakraborty C, Sarkar B, Hsu C, Wen Z, Lin C, Shieh P. Future prospects of nanoparticles on brain targeted drug delivery. J Neurooncol. 2009;93:285–6.CrossRefPubMedGoogle Scholar
  4. 4.
    Pardridge W. Blood–brain barrier delivery. Drug Discov Today. 2007;12:54–61.CrossRefPubMedGoogle Scholar
  5. 5.
    Wolburg H, Lippoldt A. Tight junctions of the blood–brain barrier: development, composition and regulation. Vascul Pharmacol. 2002;38:323–37.CrossRefPubMedGoogle Scholar
  6. 6.
    Masserini M. Nanoparticles for brain drug delivery. ISRN Biochem. 2013;2013:18.CrossRefGoogle Scholar
  7. 7.
    Garcia-Garcia E, Andrieux K, Gilb S, Couvreur P. Colloidal carriers and blood–brain barrier (BBB) translocation: a way to deliver drugs to the brain? Int J Pharm. 2005;298:274–92.CrossRefPubMedGoogle Scholar
  8. 8.
    Koffie R, Farrar C, Saidi L, William C, Hyman B, Spires-Jones T. Nanoparticles enhance brain delivery of blood–brain barrier-impermeable probes for in vivo optical and magnetic resonance imaging. Proc Natl Acad Sci U S A. 2011;108:18837–42.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Hasadsri L, Kreuter J, Hattori H, Iwasaki T, George JM. Functional protein delivery into neurons using polymeric nanoparticles. J Biol Chem. 2009;284:6972–81.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Dikpati A, Madgulkar AR, Kshirsagar SJ, Bhalekar MR, Singh Chahal A. Targeted drug delivery to CNS using nanoparticles. JAPS. 2012;2:179–91.Google Scholar
  11. 11.
    De Jonghe B, Horn C. Chemotherapy agent cisplatin induces 48-h Fos expression in the brain of a vomiting species, the house musk shrew (Suncus murinus). Am J Physiol Regul Integr Comp Physiol. 2009;296:902–11.CrossRefGoogle Scholar
  12. 12.
    Wilson JJ, Lopes JF, Lippard SJ. Synthesis, characterization, and photophysical properties of three platinum(II) complexes bearing fluorescent analogues of the Di-2-pyridylmethane ligand. Inorg Chem. 2010;49:5303–15.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Savrikar S, Lagad C. Study of preparation and standardization of ‘Maadhutailika Basti’ with special reference to emulsion stability. Ayu. 2010;31:1–6.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Fontes G, Amaral P, Nele M, Coelho M. Factorial design to optimize biosurfactant production by Yarrowia lipolytica. J Biomed Biotechnol. 2010;2010:1–8.CrossRefGoogle Scholar
  15. 15.
    Miura F, Alves M, Rocha M, Silva R, Oba-Shinjo S, Uno M, et al. Experimental model of C6 brain tumors in athymic rats Arq. Neuro-Psiquiatria. 2008;66:238–41.CrossRefGoogle Scholar
  16. 16.
    Steiniger SC, Kreuter J, Khalansky AS, Skidan IN, Bobruskin AI, Smirnova ZS, et al. Chemotherapy of glioblastoma in rats using doxorubicin-loaded nanoparticles. Int J Cancer. 2004;109:759–67.CrossRefPubMedGoogle Scholar
  17. 17.
    Sreelakshmi C, Datta KK, Yadav JS, Reddy BV. Honey derivatized Au and Ag nanoparticles and evaluation of its antimicrobial activity. J Nanosci Nanotechnol. 2011;11:6995–7000.CrossRefPubMedGoogle Scholar
  18. 18.
    Wu L, Cai X, Nelson K, Xing W, Xia J, Zhang R, et al. A green synthesis of carbon nanoparticle from honey for real-time photoacoustic imaging. Nano Res. 2013;6:312–25.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Palanisamy KL, Meenakshi Sundaram N, Devabharathi V, Thangarasu P. Synthesis and characterization of olive oil mediated iron oxide nanoparticles. Dig J Nanomater Bios. 2013;2:607–12.Google Scholar
  20. 20.
    Yan X, Gemeinhart RA. Cisplatin delivery from poly (acrylic acid-co-methyl methacrylate) microparticles. J Control Release. 2005;106:198–208.CrossRefPubMedGoogle Scholar
  21. 21.
    Ebrahimi Shahmabadi H, Akbarzadeh A, Mokhtari MJ, Mortazavi M, Ghasemi S, Mohammadi H, et al. In vitro evaluation of the effects of acetone, on the potency of cisplatin: is it a good candidate for cisplatin carrier preparation? E3 J Biotechnol Pharm Res. 2012;3:137–40.Google Scholar
  22. 22.
    Otsuka H, Nagasaki Y, Kataoka K. PEGylated nanoparticles for biological and pharmaceutical applications. Adv Drug Deliv Rev. 2012;64:246–55.CrossRefGoogle Scholar
  23. 23.
    Duan J, Zhang Y, Han S, Chen Y, Li B, Liao M, et al. Synthesis and in vitro/in vivo anti-cancer evaluation of curcumin-loaded chitosan/poly (butyl cyanoacrylate) nanoparticles. Int J Pharm. 2010;400:211–20.CrossRefPubMedGoogle Scholar
  24. 24.
    Macka M, Borák J, Seménková L, Kiss F. Decomposition of cisplatin in aqueous solutions containing chlorides by ultrasonic energy and light. J Pharm Sci. 1994;83:815–8.CrossRefPubMedGoogle Scholar
  25. 25.
    Kante B, Couvreur P, Dubois-Krack G, De Meester C, Guiot P, Roland M, et al. Toxicity of polyalkylcyanoacrylate nanoparticles I: free nanoparticles. J Pharm Sci. 1982;71:786–90.CrossRefPubMedGoogle Scholar
  26. 26.
    De Angelis LM. Brain tumours. N Engl J Med. 2001;344:114–23.CrossRefGoogle Scholar
  27. 27.
    Nelson DF, Nelson JS, Davis DR, Chang CH, Griffin TW, Pajak TF. Survival and prognosis of patients with astrocytoma with atypical or anaplastic features. J Neurooncol. 1985;3:99–103.CrossRefPubMedGoogle Scholar
  28. 28.
    Kornblith PL, Walker M. Chemotherapy for malignant gliomas. J Neurosurg. 1998;68:1–17.CrossRefGoogle Scholar
  29. 29.
    Gao H, Yang Z, Zhang S, Cao S, Shen S, Pang Z, et al. Ligand modified nanoparticles increases cell uptake, alters endocytosis and elevates glioma distribution and internalization. Sci Rep. 2013;3:2534.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Parsa AT, Chakrabarti I, Hurley PT, Chi JH, Hall JS, Kaiser MG, et al. Limitations of the C6/Wistar rat intracerebral glioma model: implications for evaluating immunotherapy. Neurosurgery. 2000;47:993–9.CrossRefPubMedGoogle Scholar
  31. 31.
    Barth R, Kaur B. Rat brain tumor models in experimental neuro-oncology: the C6, 9L, T9, RG2, F98, BT4C, RT-2 and CNS-1 gliomas. J Neurooncol. 2009;94:299–312.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Petri B, Bootz A, Khalansky A, Hekmatara T, Muller R, Uhl R. Chemotherapy of brain tumour using doxorubicin bound to surfactant-coated Poly(butyl cyanoacrylate) nanoparticles: revisiting the role of surfactants. J Control Release. 2007;117:51–8.CrossRefPubMedGoogle Scholar
  33. 33.
    Olivier JC, Fenart L, Chauvet R, Pariat C, Cecchelli R, Couet W. Indirect evidence that drug brain targeting using polysorbate 80-coated polybutylcyanoacrylate nanoparticles is related to toxicity. Pharm Res. 1999;16:1836–42.CrossRefPubMedGoogle Scholar
  34. 34.
    de Verdière AC, Dubernet C, Némati F, Soma E, Appel M, Ferté J, et al. Reversion of multidrug resistance with polyalkylcyanoacrylate nanoparticles: towards a mechanism of action. Br J Cancer. 1997;76:198–205.CrossRefPubMedGoogle Scholar
  35. 35.
    Silver DP, Richardson AL, Eklund AC, Wang ZC, Szallasi Z, Li Q, et al. Efficacy of neoadjuvant Cisplatin in triple-negative breast cancer. J Clin Oncol. 2010;28:1145–53.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Hasan Ebrahimi Shahmabadi
    • 1
  • Fatemeh Movahedi
    • 1
  • Maedeh Koohi Moftakhari Esfahani
    • 1
  • Seyed Ebrahim Alavi
    • 1
  • Ali Eslamifar
    • 2
  • Gholamreza Mohammadi Anaraki
    • 3
  • Azim Akbarzadeh
    • 1
  1. 1.Department of Pilot NanobiotechnologyPasteur Institute of IranTehranIran
  2. 2.Clinical Research DepartmentPasteur Institute of IranTehranIran
  3. 3.Tehran University of Medical SciencesTehranIran

Personalised recommendations