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 (60μL, 0.36mg 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 (400μL, 2.4mg 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.

• Authors: Ngoc Trinh Huynh, Catherine Passirani, Emilie Allard-Vannier, Laurent Lemaire, Jerome Roux, Emmanuel Garcion, Anne Vessieres, Jean-Pierre Benoit
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 423 Issue 1 Pg. 55-62 (Feb 14 2012) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 21536115 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000)
• Antineoplastic Agents
• Drug Carriers
• Ferrous Compounds
• Fluorescent Dyes
• Lipids
• Nanocapsules
• Phosphatidylethanolamines
• Plant Lectins
• Soybean Proteins
• Stearic Acids
• Triglycerides
• ferrociphenol
• soybean lectin
• Polyethylene Glycols
• Solutol HS 15

Topics

• Animals
• Antineoplastic Agents (administration & dosage, therapeutic use)
• Brain (metabolism, pathology)
• Brain Neoplasms (drug therapy, pathology)
• Drug Carriers (chemistry, toxicity)
• Female
• Ferrous Compounds (administration & dosage, therapeutic use)
• Fluorescent Dyes (administration & dosage, metabolism)
• Gliosarcoma (drug therapy, pathology)
• Hydrogen-Ion Concentration
• Infusions, Parenteral (methods)
• Injections, Intra-Arterial
• Kaplan-Meier Estimate
• Lipids (chemistry)
• Magnetic Resonance Imaging
• Magnetic Resonance Spectroscopy
• Nanocapsules (chemistry, toxicity)
• Osmolar Concentration
• Particle Size
• Phosphatidylethanolamines (chemistry)
• Plant Lectins (chemistry)
• Polyethylene Glycols (chemistry)
• Rats
• Rats, Inbred F344
• Soybean Proteins (chemistry)
• Static Electricity
• Stearic Acids (chemistry)
• Treatment Outcome
• Triglycerides (chemistry)