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Incomplete copolymer degradation of in situ chemotherapy

  • Pierre Bourdillon
  • Tanguy Boissenot
  • Lauriane Goldwirt
  • Julien Nicolas
  • Caroline Apra
  • Alexandre Carpentier
CLINICAL APPLICATIONS OF BIOMATERIAL Rapid Communication
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Part of the following topical collections:
  1. Clinical Applications of Biomaterials

Abstract

In situ carmustine wafers containing 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) are commonly used for the treatment of recurrent glioblastoma to overcome the brain-blood barrier. In theory, this chemotherapy diffuses into the adjacent parenchyma and the excipient degrades in maximum 8 weeks but no clinical data confirms this evolution, because patients are rarely operated again. A 75-year-old patient was operated twice for recurrent glioblastoma, and a carmustine wafer was implanted during the second surgery. Eleven months later, a third surgery was performed, revealing unexpected incomplete degradation of the wafer. 1H-Nuclear Magnetic Resonance was performed to compare this wafer to pure BCNU and to an unused copolymer wafer. In the used wafer, peaks corresponding to hydrophobic units of the excipient were no longer noticeable, whereas peaks of the hydrophilic units and traces of BCNU were still present. These surprising results could be related to the formation of a hydrophobic membrane around the wafer, thus interfering with the expected diffusion and degradation processes. The clinical benefit of carmustine wafers in addition to the standard radio-chemotherapy remains limited, and in vivo behavior of this treatment is not completely elucidated yet. We found that the wafer may remain after several months. Alternative strategies to deal with the blood–brain barrier, such as drug-loaded liposomes or ultrasound-opening, must be explored to offer larger drug diffusion or allow repetitive delivery.

Notes

Author contributions

PB: study concept and design/acquisition of data/analysis and interpretation/study supervision. TB: acquisition of data. LG: revision of the manuscript for important intellectual content. JN: acquisition of data/analysis and interpretation/critical revision of the manuscript for important intellectual content. CA: revision of the manuscript for important intellectual content. AC: acquisition of data/critical revision of the manuscript for important intellectual content/study supervision.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Pierre Bourdillon
    • 1
    • 2
    • 3
    • 4
  • Tanguy Boissenot
    • 5
    • 6
  • Lauriane Goldwirt
    • 7
  • Julien Nicolas
    • 5
    • 6
  • Caroline Apra
    • 2
    • 4
  • Alexandre Carpentier
    • 2
    • 4
    • 8
  1. 1.Department of Neurosurgery, Hospices Civils de LyonHospital for Neurology and Neurosurgery Pierre WertheimerLyonFrance
  2. 2.Brain and Spine Institute, INSERM U1127ParisFrance
  3. 3.Université de Lyon, Université Claude BernardLyonFrance
  4. 4.Sorbonne Universités, Université Pierre et Marie CurieParisFrance
  5. 5.Faculté de PharmacieInstitut Galien Paris-SudParisFrance
  6. 6.Université Paris-Saclay, Université Paris-sudParisFrance
  7. 7.Department of PharmacologyAssistance publique hôpitaux de Paris, Saint-Louis HospitalParisFrance
  8. 8.Department of NeurosurgeryAssistance publique hôpitaux de Paris, Pitié-Salpêtrière HospitalParisFrance

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