Treatment of 9L Gliosarcoma in Rats by Ferrociphenol-Loaded Lipid Nanocapsules Based on a Passive Targeting Strategy via the EPR Effect
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To study a passive targeting strategy, via the enhanced permeability and retention effect following systemic administration of lipid nanocapsules (LNCs) loaded with ferrociphenol, FcdiOH.
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.
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).
These results demonstrate the interesting perspectives for the systemic treatment of glioma thanks to bio-organometallic chemotherapy via lipid nanocapsules.
KEY WORDSectopic FcdiOH orthotopic PEGylated nanoparticles stealth properties
ACKNOWLEDGMENTS & DISCLOSURES
The authors would like to thank Jerome Roux (Service Commun d’Animalerie Hospitalo-Universitaire (SCAHU), Angers, France), Pascal Pigeon (CNRS, UMR 7223, Ecole Nationale Supérieure de Chimie de Paris, France), Nolwenn Lautram, Anne-Laure Laine (Inserm U646, Angers, France) and Emilie Allard (Universite de Tours, France) for their technical support. This work is supported by grants from La Ligue Nationale Contre le Cancer. Ngoc Trinh Huynh thanks the Embassy of France in Vietnam for its Evarist Galoir fellowship.
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