Advertisement

Control of doxorubicin release from magnetic Poly(dl-lactide-co-glycolide) nanoparticles by application of a non-permanent magnetic field

  • Inês N. Peça
  • A. Bicho
  • Rui Gardner
  • M. Margarida Cardoso
Research Paper

Abstract

This work studied the effect of the application time of a non-permanent magnetic field on the rate of drug release from iron oxide polymeric nanoparticles. Magnetically responsive doxorubicin loaded poly(d-lactide-co-glycolide) (PLGA) nanoparticles were synthetized by the o/w solvent extraction/evaporation method and characterized. The produced particles show spherical shapes exhibiting a size between 200 and 400 nm, a drug loading of 3.6 % (w/w) and an iron concentration of 20.7 % (w/w). Cell cytotoxicity tests showed that unloaded magnetic PLGA nanoparticles were nontoxic. Concerning the therapeutic activity, doxorubicin-loaded magnetic particles cause a remarkable enhancement of the cell inhibition rates compared to their non-magnetic counterparts (40 against 7 % of dead cells). In vitro drug release studies performed under a non-permanent magnetic field show that the application time and the on/off cycle duration have a great influence with respect to the final amount and to the rate of drug release. The final amount and the rate of doxorubicin released increase with the time of field application reaching higher values for a higher number of pulses with a lower duration. Doxorubicin release mechanism has shown to be governed by Fickian diffusion in the absence of a magnetic field while in the presence of a magnetic field some controlled relaxation polymer chains might also be present. The results show that the drug release rate from magnetic PLGA nanoparticles can be modulated through the application time and the on/off cycles duration of a non-permanent magnetic field.

Keywords

Magnetic nanoparticles Doxorubicin delivery PLGA nanoparticles Magnetically responsive drug nanoparticles Nanomedicine Health effects 

Notes

Acknowledgments

This work has been supported by Fundação para a Ciência e a Tecnologia, Portugal, through Grant No. PEst-C/EQB/LA0006/2013 and SFRH/BD/48773/2008 and contract PTDC/EQU-EPR/119631/2010. The authors would like to acknowledge Professor Ana Cecília Roque (REQUIMTE, FCT/UNL) for advice the synthesis of magnetic particles.

Supplementary material

11051_2015_3234_MOESM1_ESM.tif (143 kb)
Supplementary material 1 (TIFF 142 kb)

References

  1. Abdalla MO, Karna P, Sajja HK, Mao H, Yates C, Turner T, Aneja R (2011) Enhanced noscapine delivery using uPAR-targeted optical-MR imaging trackable nanoparticles for prostate cancer therapy. J Control Release 149:314–322CrossRefGoogle Scholar
  2. Alexiou C, Arnold W, Klein RJ, Parak FG, Hulin P, Bergemann C, Erhardt W, Wagenpfeil S, Lubbe AS (2000) Locoregional cancer treatment with magnetic drug targeting. Cancer Res 60:6641–6648Google Scholar
  3. Alexiou C, Schmid RJ, Bergemann C, Henke J, Erhardt W, Huenges E, Parak FJ (2003) Magnetic drug targeting biodistribution of the magnetic carrier and the chemotherapeutic agent mitoxantrone after locoregional cancer treatment. J Drug Target 11:139–149CrossRefGoogle Scholar
  4. Andhariya N, Chudasama B, Mehta RV, Upadhyay RV (2011) Biodegradable thermoresponsive polymeric magnetic nanoparticles: a new drug delivery platform for doxorubicin. J Nanopart Res 13:1677–1688CrossRefGoogle Scholar
  5. Artemov D (2003) Molecular magnetic resonance imaging with targeted contrast agents. J Cell Biochem 90:518–524CrossRefGoogle Scholar
  6. Bicho A, Peça IN, Roque ACA, Cardoso MM (2010) Anti-CD8 conjugated nanoparticles to target mammalian cells expressing CD8. Int J Pharm 399:80–86CrossRefGoogle Scholar
  7. Cardoso MM, Peça IN, Roque ACA (2012) Antibody-conjugated nanoparticles for therapeutic applications. Curr Med Chem 19:3103–3127CrossRefGoogle Scholar
  8. da Silva EP, Sitta DLA, Fragal VH, Cellet TSP, Mauricio MR, Garcia FP, Nakamura CV, Guilherme MR, Rubira AF, Kunita MH (2014) Covalent TiO2/pectin microspheres with Fe3O4 nanoparticles for magnetic field-modulated drug delivery. Int J Biol Macromol 67:43–52CrossRefGoogle Scholar
  9. Demarchi CA, Debrassi A, Buzzi FC, Corrêa R, Filho VC, Rodrigues CA, Nedelko N, Demchenko P, Slawska-Waniewska A, Dłuzewski P, Greneche JM (2014) A magnetic nanogel based on O-carboxymethylchitosan for antitumor drug delivery: synthesis, characterization and in vitro drug release. Soft Matter 10:3441CrossRefGoogle Scholar
  10. Ditsch A, Lindenmann S, Laibinis PE, Wang DIC, Hatton TA (2005) High-gradient magnetic separation of magnetic nanoclusters. Ind Eng Chem Res 44:6824–6836CrossRefGoogle Scholar
  11. Fang C, Kievit FM, Veiseh O, Stephen ZR, Wang T, Lee D, Ellenbogen RG, Zhang M (2012) Fabrication of magnetic nanoparticles with controllable drug loading and release through a simple assembly approach. J Control Release 162:233–241CrossRefGoogle Scholar
  12. Gonzales M, Krishnan KM (2005) Synthesis of magnetoliposomes with monodisperse iron oxide nanocrystal cores for hyperthermia. J Magn Magn Mater 293:265–270CrossRefGoogle Scholar
  13. Guilherme MR, Oliveira RS, Mauricio MR, Cellet TSP, Pereira GM, Kunita MH, Muniz EC, Rubira AF (2012) Albumin release from a brain-resembling superabsorbent magnetic hydrogel based on starch. Soft Matter 8:6629–6637CrossRefGoogle Scholar
  14. Ito A, Tanaka K, Kondo K, Shinkai M, Honda H, Matsumoto K, Saida T, Kobayashi T (2003) Tumor regression by combined immunotherapy and hyperthermia using magnetic nanoparticles in an experimental subcutaneous murine melanoma. Cancer Sci 94:308–313CrossRefGoogle Scholar
  15. Jung CW (1995) Physical and chemical properties of superparamagnetic iron oxide MR contrast agents: ferumoxides, ferumoxtran, ferumoxsil. Magn Reson Imaging 13:661–674CrossRefGoogle Scholar
  16. Kocbek P, Kralj S, Kreft ME, Krist J (2013) Targeting intracellular compartments by magnetic polymeric nanoparticles. Eur J Pharm Sci 50:130–138CrossRefGoogle Scholar
  17. Lee S-J, Jeong J-R, Shin S-C, Kim J-C, Chang Y-H, Chang Y-M, Kim JD (2004) Nanoparticles of magnetic ferric oxides encapsulated with poly(D, L latide-co-glycolide) and their application to magnetic resonance imaging contrast agent. J Magn Magn Mater 272–276:2432–2433CrossRefGoogle Scholar
  18. Li M, Neoh K-G, Wang R, Zong B-Y, Tan JY, Kang E-T (2013) Methotrexate-conjugated and hyperbranched polyglycerol-grafted Fe3O4 magnetic nanoparticles for targeted anticancer effects. Eur J Pharm Sci 48:111–120CrossRefGoogle Scholar
  19. Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L (2004) Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev 56:185–229CrossRefGoogle Scholar
  20. Monneret C (2001) Recent developments in the field of antitumor anthracyclines. Eur J Med Chem 36:483–493CrossRefGoogle Scholar
  21. Murakami H, Kobayashi M, Takeuchi H, Kawashima Y (2000) Further application of a modified spontaneous emulsification solvent diffusion method to various types of PLGA and PLA polymers for preparation of nanoparticles. Powder Technol 107:137–143CrossRefGoogle Scholar
  22. Na K, Lee ES, Bae YH (2003) Adriamycin loaded pullulan acetate/sulfonamide conjugate nanoparticles responding to tumor pH: pH dependant cell interaction, internalization and cytotoxicity. J Control Release 87:3–13CrossRefGoogle Scholar
  23. Papadimitriou S, Bikiaris D, Avgoustakis K, Karavas E, Georgarakis M (2008) Chitosan nanoparticles loaded with dorzolamide and pramipexole. Carbohydr Polym 73:44–54CrossRefGoogle Scholar
  24. Ritger PL, Peppas NA (1987) A simple equation for description of solute release II. Fickian and anomalous release from swellable devices. J Control Release 5:37–42CrossRefGoogle Scholar
  25. Roque ACA, Bispo S, Pinheiro ARN, Antunes JMA, Gonçalves D, Ferreira HA (2009) Antibody immobilization on magnetic particles. J Mol Recognit 22:77–82CrossRefGoogle Scholar
  26. Santos DP, Ruiz MA, Gallardo V, Zanoni MVB, Arias JL (2011) Multifunctional antitumor magnetite/chitosan-l-glutamic acid (core/shell) nanocomposites. J Nanopart Res 13:4311–4323CrossRefGoogle Scholar
  27. Seo SB, Yang J, Hyung W, Cho E-J, Lee T-I, Song YJ, Yoon H-G, Suh J-S, Huh Y-M, Haam S (2007) Novel multifunctional PHDCA/PEI nano-drug carriers for simultaneous magnetically targeted cancer therapy and diagnosis via magnetic resonance imaging. Nanotechnology 18:1–8CrossRefGoogle Scholar
  28. Tansik G, Yakar A, Gunduz U (2014) Tailoring magnetic PLGA nanoparticles suitable for doxorubicin delivery. J Nanopart Res 16:2171–2177CrossRefGoogle Scholar
  29. Wang J, Gong C, Wang Y, Wu G (2014) Magnetic nanoparticles with a pH-sheddable layer for antitumor drug delivery. Colloid Surf B 118:218–225CrossRefGoogle Scholar
  30. Yang J, Lee C-H, Park J, Seo S, Lim E-K, Song YJ, Suh J-S, Yoon H-G, Huh Y-M, Haam S (2007) Antibody conjugated magnetic PLGA nanoparticles for diagnosis and treatment of breast cancer. J Mater Chem 17:2695–2699CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Inês N. Peça
    • 1
  • A. Bicho
    • 2
  • Rui Gardner
    • 2
  • M. Margarida Cardoso
    • 1
  1. 1.LAQV, REQUIMTE, Departamento de Química, Faculdade de Ciências e TecnologiaUniversidade Nova de LisboaCaparicaPortugal
  2. 2.Instituto Gulbenkian de CiênciaOeirasPortugal

Personalised recommendations