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 o...

Full description

Saved in:
Bibliographic Details
Published in:Pharmaceutical research 2011-12, Vol.28 (12), p.3189-3198
Main Authors: Huynh, Ngoc Trinh, Morille, Marie, Bejaud, Jerome, Legras, Pierre, Vessieres, Anne, Jaouen, Gerard, Benoit, Jean-Pierre, Passirani, Catherine
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - therapeutic use
Biochemistry
Biological and medical sciences
Biomedical and Life Sciences
Biomedical Engineering and Bioengineering
Biomedicine
Brain - drug effects
Brain Neoplasms - drug therapy
Drug Delivery Systems
Female
Ferrous Compounds - administration & dosage
Ferrous Compounds - therapeutic use
General pharmacology
Gliosarcoma - drug therapy
Life Sciences
Lipids
Lipids - chemistry
Medical Law
Medical sciences
Nanocapsules - chemistry
Nanoparticles
Pharmaceutical sciences
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Pharmacology/Toxicology
Pharmacy
Polyethylene glycol
Polyethylene Glycols - chemistry
Rats
Rats, Inbred F344
Research Paper
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0724-8741
1573-904X
1573-904X
DOI:10.1007/s11095-011-0501-y