Treatment of 9L gliosarcoma in rats by ferrociphenol-loaded lipid nanocapsules based on a passive targeting strategy via the EPR effect.

Abstract

PURPOSE:

To study a passive targeting strategy, via the enhanced permeability and retention effect following systemic administration of lipid nanocapsules (LNCs) loaded with ferrociphenol, FcdiOH.

METHODS:

Long chains of polyethylene glycol (DSPE-mPEG2000) were incorporated onto the surface of LNCs by post-insertion technique. Stealth properties of LNCs were investigated by in vitro complement consumption and macrophage uptake, and in vivo pharmacokinetics in healthy rats. Antitumour effect of FcdiOH-loaded LNCs was evaluated in subcutaneous and intracranial 9L gliosarcoma rat models.

RESULTS:

LNCs and DSPE-mPEG2000-LNCs presented low complement activation and weak macrophage uptake. DSPE-mPEG2000-LNCs exhibited prolonged half-life and extended area under the curve in healthy rats. In a subcutaneous gliosarcoma model, a single intravenous injection of FcdiOH-LNCs (400 μL, 2.4 mg/rat) considerably inhibited tumour growth when compared to the control. DSPE-mPEG2000-FcdiOH-LNCs exhibited a strong antitumour effect by nearly eradicating the tumour by the end of the study. In intracranial gliosarcoma model, treatment with DSPE-mPEG2000-FcdiOH-LNCs and FcdiOH-LNCs statistically improved median survival time (28 and 27.5 days, respectively) compared to the control (25 days).

CONCLUSION:

These results demonstrate the interesting perspectives for the systemic treatment of glioma thanks to bio-organometallic chemotherapy via lipid nanocapsules.

• Authors: Ngoc Trinh Huynh, Marie Morille, Jerome Bejaud, Pierre Legras, Anne Vessieres, Gerard Jaouen, Jean-Pierre Benoit, Catherine Passirani
• Journal: Pharmaceutical research (Pharm Res) Vol. 28 Issue 12 Pg. 3189-98 (Dec 2011) ISSN: 1573-904X [Electronic] United States
• PMID: 21691892 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Ferrous Compounds
• Lipids
• Nanocapsules
• ferrociphenol
• Polyethylene Glycols

Topics

• Animals
• Antineoplastic Agents (administration & dosage, therapeutic use)
• Brain (drug effects)
• Brain Neoplasms (drug therapy)
• Drug Delivery Systems
• Female
• Ferrous Compounds (administration & dosage, therapeutic use)
• Gliosarcoma (drug therapy)
• Lipids (chemistry)
• Nanocapsules (chemistry)
• Polyethylene Glycols (chemistry)
• Rats
• Rats, Inbred F344