Pharmaceutical Chemistry Journal

, Volume 42, Issue 6, pp 363–367

Radiation sterilization of medicinal formulations of doxorubicin bound to poly(butylcyanoacrylate) nanoparticles

  • O. O. Maksimenko
  • E. P. Pavlov
  • É. G. Tushov
  • A. A. Molin
  • Yu. V. Stukalov
  • T. N. Prudskova
  • P. G. Sveshnikov
  • J. Kreuter
  • S. É. Gel’perina
Drug Synthesis Methods and Manufacturing Technology

Abstract

Polybutylcyanoacrylate nanoparticles represent a potential system for delivering medicinal agents. The present report describes development of a method for radiation sterilization of medicinal formulations of doxorubicin based on polybutylcyanoacrylate nanoparticles. The physicochemical properties of the medicinal formulation were studied after gamma irradiation and irradiation with accelerated electrons over the dose range 10–35 kGy. The chemical structure of doxorubicin and the polymer carrier was found to be intact after irradiation at a dose of 25 kGy. Irradiation at these doses also had no effect on the colloidal properties of polymer nanoparticles, which retained their stability to aggregation and sedimentation. The optimum sterilizing dose was 15 kGy.

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References

  1. 1.
    S. M. Moghimi, A. C. Hunter, and J. C. Murray, FASEB J., 19(3), 311–330 (2005).PubMedCrossRefGoogle Scholar
  2. 2.
    S.-S. Ferig and S. Chien, Chem. England. Sci., 58, 4087–4114 (2003).CrossRefGoogle Scholar
  3. 3.
    I. Brigger, C. Bubernet, and P. Couvreur, Adv. Drug Deliv. Rev., 54(5), 631–651 (2002).PubMedCrossRefGoogle Scholar
  4. 4.
    A. E. Gulyaev, S. E. Gelperina, I. N. Skidan, et al., Pharm. Res., 16(10), 1564–1569 (1999).PubMedCrossRefGoogle Scholar
  5. 5.
    S. C. J. Steiniger, J. Kreuter, A. S. Khalansky, et al., Int. J. Cancer, 109(5), 159–167 (2004).CrossRefGoogle Scholar
  6. 6.
    S. E. Gelperina, A. S. Khalansky, I. N. Skidan, et al., Toxicol. Lett., 126(2), 131–142 (2002).PubMedCrossRefGoogle Scholar
  7. 7.
    J. Kattan, J.-P. Droz, P. Couvreur, et al., Invest. New Drugs, 10(3), 191–199 (1992).PubMedCrossRefGoogle Scholar
  8. 8.
    E. Pereverzeva, I. Treschalin, D. Bodygin, et al., J. Control. Release (2006) (in press).Google Scholar
  9. 9.
    C. Vauthier, E. Dubernet, E. Fattal, et al., Adv. Drug Deliv. Rev., 55(4), 519–548 (2003).PubMedCrossRefGoogle Scholar
  10. 10.
    Handbook for Normative-Methodological Documents, Regulations for Radiation Sterilization of Medical Materials and Products [in Russian], Moscow (1980). Methods 1.5.2 and 1.5.3.Google Scholar
  11. 11.
    Method for Estimating Initial Contamination of Products Sterilized by Radiation [in Russian], Ratified by the Ministry of Health, 00.02.82, Regulation No. 2535-82, Moscow (1982).Google Scholar
  12. 12.
    Methodological Guide for the Use of an Indirect Method of Estimating Radioresistant Industrial Microflora at Establishments Producing Radiation Sterilized Products [in Russian], Ratified by the Ministry of Health, 10.10.90, Regulation No. 15-6 / 37, Moscow (1990).Google Scholar
  13. 13.
    I. I. Samoilenko, E. P. Pavlov, and É. G. Tushov, Khim.-Farm. Zh., 2(5), 617–619 (1988).Google Scholar
  14. 14.
    Encyclopedia of Polymers [in Russian], Sovetskaya Éntsiklopediya (1977), pp. 871–872.Google Scholar
  15. 15.
    P. Sommerfeld, U. Schroeder, and B. Sabel, Int. J. Pharm., 164(2), 113–118 (1998).CrossRefGoogle Scholar
  16. 16.
    C. Verdun, P. Couvreur, H. Vranckx, et al., J. Control. Rel., 3(2), 205–208 (1986).CrossRefGoogle Scholar
  17. 17.
    M. Fouarge, M. Dewulf, P. Couvreur, et al., J. Microencapsulation, 6(1), 29–34 (1989).PubMedCrossRefGoogle Scholar
  18. 18.
    A. K. Pikaev, Current Radiation Chemistry. Solid Bodies and Polymers. Applied Aspects [in Russian], Nauka, Moscow (1987).Google Scholar
  19. 19.
    V. K. Milinchuk, É. R. Klinshpont, and V. I. Tupikov, Basic Radiation Resistance of Organic Materials [in Russian], Énergoatomizdat, Moscow (1994), pp. 142–147.Google Scholar
  20. 20.
    D. V. Paramonov, E. A. Antonova, N. G. Zharova, et al., Khim.-Farm. Zh., 30(10), 42–45 (1996).Google Scholar
  21. 21.
    USSR State Pharmacopeia [in Russian], 11th Edition, Part 2, Meditsina, Moscow (1989), p. 24.Google Scholar

Copyright information

© Springer Science+Business Media, Inc. 2008

Authors and Affiliations

  • O. O. Maksimenko
    • 1
  • E. P. Pavlov
    • 2
  • É. G. Tushov
    • 3
  • A. A. Molin
    • 2
  • Yu. V. Stukalov
    • 1
  • T. N. Prudskova
    • 3
  • P. G. Sveshnikov
    • 1
  • J. Kreuter
    • 4
  • S. É. Gel’perina
    • 1
  1. 1.All-Russian Scientific Center for Molecular Diagnosis and TreatmentMoscowRussia
  2. 2.State Scientific Center “Institute of Biophysics”Ministry of Health of the Russian FederationMoscowRussia
  3. 3.OAO G. S. Petrov Science Research Institute of PlasticsMoscowRussia
  4. 4.Institute of Pharmaceutical TechnologyJ. W. Goethe UniversityFrankfurtGermany

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