AAPS PharmSciTech

, 9:718 | Cite as

γ-Irradiation of PEGd,lPLA and PEG-PLGA Multiblock Copolymers: I. Effect of Irradiation Doses

  • R. Dorati
  • C. Colonna
  • M. Serra
  • I. Genta
  • T. Modena
  • F. Pavanetto
  • P. Perugini
  • B. Conti
Research Article


To evaluate the effects of different gamma irradiation doses on PEGd,lPLA and PEG-PLGA multiblock copolymers. The behaviour of the multiblock copolymers to irradiation was compared to that of PLA, PLGA polymers. PEGd,lPLA, PEG-PLGA, PLA and PLGA polymers were irradiated by using a 60Co irradiation source at 5, 15, 25 and 50 kGy total dose. Characterization was performed on all samples before and after irradiation, by nuclear magnetic resonance (NMR), infrared absorption spectrophotometry (FTIR) and gel permeation chromatography (GPC). The effect of gamma irradiation on polymer stability was also evaluated. Results of NMR and FTIR suggest an increase in -OH and -COOH groups, attributed to scission reactions induced by irradiation treatment. Data of GPC analysis showed that the weight average molecular weight (Mw) of polymer samples decreased with increasing irradiation dose. The extent of Mw degradation expressed as percentage of Mw reduction was more prominent for polymers with high molecular weight as PEGd,lPLA and PLA. The dominant effect of gamma-irradiation on both polymer samples was chain scission. The multiblock copolymer PEGd,lPLA presented higher sensitivity to irradiation treatment with respect to PLA, likely due to the presence of PEG in the matrix. The effect of gamma irradiation continues over a much longer period of time after gamma irradiation has been performed. It is suggested that the material reacts with oxygen to form peroxyl free radicals, which may further undergo degradation reactions during storage after irradiation.

Key words

gamma-radiations G(s) and G(xmultiblock copolymers polymer stability 


  1. 1.
    C. Martinez-Sancho, R. Herrero-Vanrell, and S. Negro. Study of gamma-irradiation effects on acyclovir poly(D,L-lactic-co-glycolic)acid microspheres for intravitreal administration. J. Control Release. 99:41–52 (2004).PubMedCrossRefGoogle Scholar
  2. 2.
    M. B. Sintzel, A. Merkli, C. Tabatabay, and R. Gurny. Influence of irradiation sterilization on polymers used as drug carriers—a review. Drug Dev. Ind. Pharm. 23(9):857–879 (1997).CrossRefGoogle Scholar
  3. 3.
    A. G. Hausberger, R. A. Kenley, and P. P. DeLuca. Gamma irradiation effects on molecular weight and in vitro degradation of poly(dl-lactide-co-glycolide) microparticles. Pharm. Res 12(6):851–856 (1995).PubMedCrossRefGoogle Scholar
  4. 4.
    L. Montanari, F. Cilurzo, F. Selmin, B. Conti, I. Genta, G. Poletti, F. Orsini, and L. Valvo. Poly(lactide-co-glycolide) microspheres containing bupivacaine: comparison between gamma and beta irradiation effects. J. Control Release 90(3):281–290 (2003).PubMedCrossRefGoogle Scholar
  5. 5.
    J. A. Bushell, M. Claybourn, H. E. Williams, and D. M. Murphy. An EPR and ENDOR study of γ and β-radiation sterilization in poly(lactide-co-glycolide) polymers and microspheres. J. Control Release. 110:49–57 (2005).PubMedCrossRefGoogle Scholar
  6. 6.
    R. Dorati, I. Genta, L. Montanari, A. Buttafava, A. Faucitano, and B. Conti. The effect of γ-irradiation on PLGA/PEG microspheres containing ovalbumin. J. Control Release. 107:78–90 (2005).PubMedCrossRefGoogle Scholar
  7. 7.
    A. Faucitano, A. Buttafava, L. Montanari, F. Cilurzo, B. Conti, I. Genta, and L. Valvo. Radiation induced free radical reactions in polymer/drug systems for controlled release: an EPR investigation. Radiat. Phys. Chem. 67:61–72 (2003).CrossRefGoogle Scholar
  8. 8.
    L. Montanari, M. Costantini, E. C. Signoretti, L. Valvo, M. Santucci, M. Bortolomei, P. Fattibene, S. Onori, A. Faucitano, B. Conti, and I. Genta. Gamma-irradiations effects on poly(d,l-lactide-co-glycolide) microspheres. J. Control Release. 56(2):219–229 (1998).PubMedCrossRefGoogle Scholar
  9. 9.
    K. J. Hemmerich. Radiation sterilization—polymer materials selection for radiation-sterilized products. MDDI Feb. 2000: p. 78.Google Scholar
  10. 10.
    H. J. Haugen, M. Brunner, F. Pellkofer, J. Aigner, J. Will, and E. Wintermantel. Effect of different γ-irradiation doses on cytotoxicity and material properties of porous polyether-urethane polymer. J. Biomed. Mater. Res. B Appl. Biomater. 80B(2):415–423 (2006).Google Scholar
  11. 11.
    M. Claybourn, H. Gray, D. M. Murphy, I. J. Purnell, and C. C. Rowlands. Electron magnetic resonance study of gamma-irradiated poly(lactide-co-glycolide) microspheres. J. Control Release. 91:431–438 (2003).PubMedCrossRefGoogle Scholar
  12. 12.
    The use of ionizing radiation in the manufacture of medicinal products European Guidelines 3AQ4a.Google Scholar
  13. 13.
    A. Gèze, M. C. Venier-Julienne, J. Cottin, N. Faisant, and J. P. Benoit. PLGA microsphere bioburden evaluation for radiosterilization dose selection. J. Microencapsul 18(5):627–636 (2001).PubMedCrossRefGoogle Scholar
  14. 14.
    Y. Y. Huang, and T. W. Chung. Microencapsulation of gentamicin in biodegradable PLA and/or PLA/PEG copolymer. J. Microencapsul. 18(4):457–465 (2001).Google Scholar
  15. 15.
    R. Quesnel, and P. Hildgen. Synthesis of PLA-b-PEG multiblock copolymers for stealth drug carrier preparation. Molecules. 10:98–104 (2005).PubMedCrossRefGoogle Scholar
  16. 16.
    T. Panoyan, R. Quesnel, and P. Hildgen. Injectable nanospheres from a novel multiblock copolymer: cytocompatibility, degradation and in vitro release studies. J. Microencapsul 20(6):745–758 (2003).PubMedCrossRefGoogle Scholar
  17. 17.
    B. Fayolle, L. Audouin, and J. Verdu. Radiation induced embrittlement of PTFE. Polymer. 44:2773–2780 (2003).CrossRefGoogle Scholar
  18. 18.
    B. Fayolle, X. Colin, L. Audouin, and J. Verdu. Mechanism of degradation induced embrittlement in polyethylene. Polym. Degrad. Stab. 92:231–238 (2007).CrossRefGoogle Scholar
  19. 19.
    K. Nakane, Y. Hata, K. Morita, T. Ogihara, and N. Ogata. Porous poly(L-lactic acid)/poly(ethylene glycol) blend films. J. Appl. Polym. Sci 94(3):965–970 (2004).CrossRefGoogle Scholar
  20. 20.
    R. L. Cleek, K. C. Ting, S. G. Eskin, and A. G. Mikos. Microparticles of poly(d,l-lactic-co-glycolic acid)/poly(ethyleneglycol) blends for controlled drug delivery. J. Control Release. 48:259–268 (1997).CrossRefGoogle Scholar
  21. 21.
    C. L. Moad, and D. J. Winzor. Quantitative characterization of radiation degradation in polymers by evaluation of scission and cross-linking yields. Prog. Polym. Sci. 23:759–813 (1998).CrossRefGoogle Scholar
  22. 22.
    S. Devasahayam, D. J. T. Hill, and A. K. Whittaker. G values for scission and crosslinking on γ-radiolysis of Ultem at 303K. High Perform Polym. 15:259–267 (2003).CrossRefGoogle Scholar
  23. 23.
    P. Nugroho, H. Mitomo, F. Yoshii, and T. Kume. Degradation of poly(L-lactic acid) by γ-irradiation. Polym. Degrad. Stab. 72:337–343 (2001).CrossRefGoogle Scholar
  24. 24.
    J. S. C. Loo, C. P. Ooi, and F. Y. C Boey. Degradation of poly(lactide-co-glycolide) (PLGA) and poly(L-lactide) (PLLA) by electron beam radiation. Biomaterials. 26:1359–1367 (2005).PubMedCrossRefGoogle Scholar
  25. 25.
    M. Sen, C. Uzun, Ö . Kantoglu, S. M. Erdogan, V. Deniz, and O. Guven. Effect of gamma irradiation conditions on the radiation-induced degradation of isobutylene-isoprene rubber. Nucl. Instrum. Methods Phys. Res. B. 203:480–484 (2008).Google Scholar
  26. 26.
    C. Volland, M. Wolff, and T. Kissel. The influence of terminal gamma sterilization on captopril containing poly(D,L-lactide-co-glycolide) microspheres. J. Control. Release. 31:293–305 (1994).CrossRefGoogle Scholar
  27. 27.
    D. Mohr, M. Wolff, and T. Kissel. Gamma irradiation for terminal sterilization of 17β-estradiol loaded poly(D,L-lactide-co-glycolide) microparticles. J. Control. Release. 61:203–217 (1999).PubMedCrossRefGoogle Scholar
  28. 28.
    L. Montanari, F. Cilurzo, L. Valvo, A. Faucitano, A. Buttafava, A. Groppo, I. Genta, and B. Conti. Gamma irradiation effects on stability of poly(lactide-co-glycolide) microspheres containing clonazepam. J. Control. Release. 75:317–330 (2001).PubMedCrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2008

Authors and Affiliations

  • R. Dorati
    • 1
  • C. Colonna
    • 1
  • M. Serra
    • 1
  • I. Genta
    • 1
  • T. Modena
    • 1
  • F. Pavanetto
    • 1
  • P. Perugini
    • 1
  • B. Conti
    • 1
  1. 1.Department of Pharmaceutical ChemistryUniversity of PaviaPaviaItaly

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