title: Treatment of 9L gliosarcoma in rats by ferrociphenol-loaded lipid nanocapsules based on a passive targeting strategy via the EPR effect.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  These results demonstrate the interesting perspectives for the systemic treatment of glioma thanks to bio-organometallic chemotherapy via lipid nanocapsules.
authors.affiliation: LUNAM Université, Ingénierie de la Vectorisation Particulaire, 49933 Angers, France.
authors.forename: Ngoc Trinh
authors.initials: NT
authors.lastname: Huynh
authors.forename: Marie
authors.initials: M
authors.lastname: Morille
authors.forename: Jerome
authors.initials: J
authors.lastname: Bejaud
authors.forename: Pierre
authors.initials: P
authors.lastname: Legras
authors.forename: Anne
authors.initials: A
authors.lastname: Vessieres
authors.forename: Gerard
authors.initials: G
authors.lastname: Jaouen
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Benoit
authors.forename: Catherine
authors.initials: C
authors.lastname: Passirani
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy*; D016503:Drug Delivery Systems; D005260:Female; D005296:Ferrous Compounds / Q000008:administration & dosage* / Q000627:therapeutic use*; D018316:Gliosarcoma / Q000188:drug therapy*; D008055:Lipids / Q000737:chemistry; D053769:Nanocapsules / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D000970:Antineoplastic Agents; D005296:Ferrous Compounds; D008055:Lipids; D053769:Nanocapsules; C533771:ferrociphenol; D011092:Polyethylene Glycols