Journal
PHARMACEUTICAL RESEARCH
Volume 27, Issue 1, Pages 56-64Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-009-0006-0
Keywords
convection-enhanced delivery; glioma; iron; lipid nanocapsules; radiotherapy
Funding
- Region des Pays de la Loire
- Canceropole Grand Ouest
- La Ligue Nationale Contre le Cancer
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Purpose. The goal of the present study was to evaluate the efficacy of a new organometallic drug, ferrociphenol (Fc-diOH), in combination with external radiotherapy in intracerebral 9L glioma model. We tested the hypothesis that the combination of external radiotherapy with Fc-diOH could potentiate the action of this drug. Methods. 9L cells were treated with Fc-diOH-LNCs (from 0.01 to 1 mu mol/L) and irradiated with external radiotherapy (from 2 to 40 Gy). In vivo assessment was evaluated by the inoculation of 9L cells in Fisher rats. Chemotherapy with Fc-diOH-LNCs (0.36 mg/rat) was administered by means of convection-enhanced delivery (CED), and the treatment was followed by three irradiations of 6 Gy doses (total dose=18 Gy). Results. In vitro evaluations evidenced that a combined treatment with Fc-diOH-LNCs and irradiations showed synergistic antitumor activity on 9L cells. Combining cerebral irradiation with CED of Fc-diOH-LNCs led to a significantly longer survival and the existence of long-term survivors compared to Fc-diOH-LNCs-treated animals (p<0.0001) and to the group treated with blank LNCs + radiotherapy (p=0.0079). Conclusion. The synergistic effect between ferrociphenol-loaded LNCs and radiotherapy was due to a closely oxidative relationship. Upon these considerations, Fc-diOH-LNCs appear to be an efficient radiosensitive anticancer drug delivery system.
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