Administration-dependent efficacy of ferrociphenol lipid nanocapsules for the treatment of intracranial 9L rat gliosarcoma

Abstract : The anti-tumour effect of ferrociphenol (FcdiOH)-loaded lipid nanocapsules (LNCs), with or without a DSPE-mPEG2000 coating, was evaluated on an orthotopic gliosarcoma model after administration by convection-enhanced delivery (CED) technique or by intra-carotid injection. No toxicity was observed by MRI nor by MRS in healthy rats receiving a CED injection of FcdiOH-LNCs (60 μL, 0.36 mg of FcdiOH/rat) when the pH and osmolarity had been adjusted to physiological values prior to injection. At this dose, the treatment by CED with FcdiOH-LNCs significantly increased the survival time of tumour-bearing rats in comparison with an untreated group (28.5 days vs 25 days, P = 0.0009) whereas DSPE-mPEG2000–FcdiOH-LNCs did not exhibit any efficacy with a median survival time of 24 days. After intra-carotid injection (400 μL, 2.4 mg of FcdiOH/rat), hyperosmolar DSPE-mPEG2000–FcdiOH-LNCs markedly increased the median survival time (up to 30 days, P = 0.0008) as compared to the control (20%). This was strengthened by their evidenced accumulation in the tumour zone and by the measure of the fluorescent brain surface obtained on brain slides for these DiI-labelled LNCs, being 3-fold higher than for the control. These results demonstrated that, depending upon the administration route used, the characteristics of LNC suspensions had to be carefully adapted.
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Submitted on : Thursday, August 30, 2018 - 4:32:39 PM
Last modification on : Tuesday, May 7, 2019 - 6:30:20 PM

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Ngoc Trinh Huynh, Catherine Passirani, Émilie Allard-Vannier, Laurent Lemaire, Jerome Roux, et al.. Administration-dependent efficacy of ferrociphenol lipid nanocapsules for the treatment of intracranial 9L rat gliosarcoma. International Journal of Pharmaceutics, Elsevier, 2012, 423 (1), pp.55 - 62. ⟨10.1016/j.ijpharm.2011.04.037⟩. ⟨hal-01865009⟩

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