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In vivo evaluation of intracellular drug-nanocarriers infused into intracranial tumours by convection-enhanced delivery: distribution and radiosensitisation efficacy

  • Laboratory Investigation - Human/Animal Tissue
  • Published:
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Abstract

The objective of the present study was to investigate the interest of convection-enhanced delivery (CED) for the administration of a nanocarrier-based radiosensitizing chemotherapy in the rat brain. Pursuing on newly developed lipid nanocapsules (LNC) that can be internalised within brain tumour cells, we studied their intracerebral distribution when labelled with fluorescent Nile red (NR). As paclitaxel (Px) represents an interesting radiosensitiser, we also evaluated the potential radiosensitising effects of Px-loaded LNC administered through CED in the 9L intracranial rat glioblastoma model. The distribution study demonstrated that CED injection of NR-loaded LNC (NR-LNC) improved significantly the volume of distribution of NR when matched with simple injection (by about 150 fold). It also reveals that the LNC perfusion of a whole tumour forming area inside the CNS (6 days after implantation of 103 9L cells) is achievable through CED injection, whilst preserving the ability of LNC to reach the intracellular space of encountered tumour cells. Having established an animal model of encephalic irradiation close to the clinic (18 Gray in three fractions of six Gray at days 8, 11 and 14 after 9L cell implantation) we proved the feasibility of the combination of CED for the administration of drug-loaded LNC with external beam therapy. Although a single CED injection of Px-LNC at low Px dose (375 μg/kg of bodyweight) gave the best median survival (twice that of untreated controls), it underlines the need for optimisation. Hence, the possibility of grafting recognition moieties onto the LNC surface combined to their biocompatibility must be beneficial.

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Acknowledgments

This work was supported by funding from the Institut National de la Santé et de la Recherche Médicale, from the Cancéropôle Grand Ouest, from the Ligue Nationale Contre le Cancer (Equipe Labellisée 2007) and from the Comité Départemental de Maine et Loire de la Ligue Contre le Cancer through a PhD fellowship to Archibald Paillard. We are also grateful to Pierre Legras and Jérôme Roux from the Service Commun d’Animalerie Hospitalo-Universitaire (SCAHU, Angers, France) for skilful technical support.

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Authors and Affiliations

  1. Inserm U646, Université d’Angers, 10 rue André Boquel, 49100, Angers, France

    Sandrine Vinchon-Petit, Archibald Paillard, Jean-Pierre Benoit, Emmanuel Garcion & Philippe Menei

  2. DĂ©partement de Neurochirurgie, CHU, 4 rue Larrey, 49033, Angers, France

    Philippe Menei

  3. Centre RĂ©gional de Lutte Contre le Cancer, Centre Paul Papin, 2 rue Moll, 49933, Angers, France

    Delphine Jarnet

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  1. Sandrine Vinchon-Petit
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  2. Delphine Jarnet
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  3. Archibald Paillard
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  4. Jean-Pierre Benoit
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  5. Emmanuel Garcion
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  6. Philippe Menei
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Correspondence to Emmanuel Garcion.

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Vinchon-Petit, S., Jarnet, D., Paillard, A. et al. In vivo evaluation of intracellular drug-nanocarriers infused into intracranial tumours by convection-enhanced delivery: distribution and radiosensitisation efficacy. J Neurooncol 97, 195–205 (2010). https://doi.org/10.1007/s11060-009-0012-4

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  • DOI: https://doi.org/10.1007/s11060-009-0012-4

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