Local delivery of ferrociphenol lipid nanocapsules followed by external radiotherapy as a synergistic treatment against intracranial 9L glioma xenograft.

Abstract

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 micromol/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.

• Authors: Emilie Allard, Delphine Jarnet, Anne Vessières, Sandrine Vinchon-Petit, Gérard Jaouen, Jean-Pierre Benoit, Catherine Passirani
• Journal: Pharmaceutical research (Pharm Res) Vol. 27 Issue 1 Pg. 56-64 (Jan 2010) ISSN: 1573-904X [Electronic] United States
• PMID: 19908129 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Ferrous Compounds
• Nanocapsules
• ferrociphenol

Topics

• Animals
• Antineoplastic Agents (administration & dosage, chemistry, therapeutic use)
• Brain Neoplasms (drug therapy, mortality, radiotherapy)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Combined Modality Therapy (methods)
• Cranial Irradiation (methods)
• Female
• Ferrous Compounds (administration & dosage, chemistry, therapeutic use)
• Glioma (drug therapy, mortality, radiotherapy)
• Infusions, Intralesional
• Nanocapsules (administration & dosage, chemistry, therapeutic use)
• Rats
• Rats, Inbred F344
• Xenograft Model Antitumor Assays