title: 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.affiliation: LUNAM Université, Ingénierie de la Vectorisation Particulaire, F-49933 Angers, France.
authors.forename: Ngoc Trinh
authors.initials: NT
authors.lastname: Huynh
authors.forename: Catherine
authors.initials: C
authors.lastname: Passirani
authors.forename: Emilie
authors.initials: E
authors.lastname: Allard-Vannier
authors.forename: Laurent
authors.initials: L
authors.lastname: Lemaire
authors.forename: Jerome
authors.initials: J
authors.lastname: Roux
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Garcion
authors.forename: Anne
authors.initials: A
authors.lastname: Vessieres
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Benoit
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004337:Drug Carriers / Q000737:chemistry / Q000633:toxicity; D005260:Female; D005296:Ferrous Compounds / Q000008:administration & dosage* / Q000627:therapeutic use*; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000378:metabolism; D018316:Gliosarcoma / Q000188:drug therapy* / Q000473:pathology; D006863:Hydrogen-Ion Concentration; D007263:Infusions, Parenteral / Q000379:methods; D007269:Injections, Intra-Arterial; D053208:Kaplan-Meier Estimate; D008055:Lipids / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D053769:Nanocapsules / Q000737:chemistry* / Q000633:toxicity; D009994:Osmolar Concentration; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry; D037121:Plant Lectins / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D011916:Rats, Inbred F344; D030262:Soybean Proteins / Q000737:chemistry; D055672:Static Electricity; D013229:Stearic Acids / Q000737:chemistry; D016896:Treatment Outcome; D014280:Triglycerides / Q000737:chemistry; D010835:Phytohemagglutinins
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D005296:Ferrous Compounds; D005456:Fluorescent Dyes; D008055:Lipids; D053769:Nanocapsules; D010714:Phosphatidylethanolamines; D037121:Plant Lectins; D011092:Polyethylene Glycols; D030262:Soybean Proteins; D013229:Stearic Acids; D014280:Triglycerides; C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); C533771:ferrociphenol; C028824:soybean lectin; D010835:Phytohemagglutinins; C067028:Solutol HS 15