title: Conventional versus stealth lipid nanoparticles: formulation and in vivo fate prediction through FRET monitoring.
abstract: The determination of the nanocarrier fate in preclinical models is required before any translation from laboratory to clinical trials. Modern fluorescent imaging techniques have gained considerable advances becoming a powerful technology for non-invasive visualization in living subjects. Among them, Forster (fluorescence) resonance energy transfer (FRET) is a particular fluorescence imaging which involves energy transfer between 2 fluorophores in a distance-dependent manner. Considering this feature, the encapsulation of an acceptor/donor pair in lipid nanoparticles (LNEs: lipid nanoemulsions, LNCs: lipid nanocapsules) allowed the carrier integrity to be tracked. Accordingly, we used this FRET technique to evaluate the behavior of LNEs, conventional LNCs and newly designed stealth LNCs. After the development through a one-step (OS) PEGylation process of these stealth LNCs (OS LNCs), in vitro guest exchange dynamics and release kinetics were evaluated for both LNC formulations. We thereafter assessed in vivo biodistribution of all types of lipid nanoparticles. Results showed enhanced stability of encapsulation in OS LNCs in comparison to conventional LNCs. Additionally, the presence of the long PEG chains on the lipid nanoparticle surface altered the biodistribution pattern. Despite different release kinetic profiles, OS LNCs and LNEs showed extended blood circulation time associated with a good structure stability over several hours after intravenous injection.
authors.affiliation: LUNAM Université - Micro et Nanomédecines Biomimétiques, F-49933 Angers, France; INSERM U1066, IBS-CHU, 4 Rue Larrey, F-49933 Angers Cedex 9, France.
authors.forename: A-L
authors.initials: AL
authors.lastname: Lainé
authors.affiliation: INSERM U823, Institut Albert Bonniot, F-38 706 Grenoble, France; Université Joseph Fourier, F-38706 Grenoble, France; CEA, LETI, DTBS, 17 Avenue des Martyrs, F-38054 Grenoble Cedex 9, France.
authors.forename: J
authors.initials: J
authors.lastname: Gravier
authors.affiliation: INSERM U823, Institut Albert Bonniot, F-38 706 Grenoble, France; Université Joseph Fourier, F-38706 Grenoble, France.
authors.forename: M
authors.initials: M
authors.lastname: Henry
authors.affiliation: INSERM U823, Institut Albert Bonniot, F-38 706 Grenoble, France; Université Joseph Fourier, F-38706 Grenoble, France.
authors.forename: L
authors.initials: L
authors.lastname: Sancey
authors.affiliation: LUNAM Université - Micro et Nanomédecines Biomimétiques, F-49933 Angers, France; INSERM U1066, IBS-CHU, 4 Rue Larrey, F-49933 Angers Cedex 9, France.
authors.forename: J
authors.initials: J
authors.lastname: Béjaud
authors.affiliation: LUNAM Université - Micro et Nanomédecines Biomimétiques, F-49933 Angers, France; INSERM U1066, IBS-CHU, 4 Rue Larrey, F-49933 Angers Cedex 9, France.
authors.forename: E
authors.initials: E
authors.lastname: Pancani
authors.affiliation: LUNAM Université - Micro et Nanomédecines Biomimétiques, F-49933 Angers, France; INSERM U1066, IBS-CHU, 4 Rue Larrey, F-49933 Angers Cedex 9, France.
authors.forename: M
authors.initials: M
authors.lastname: Wiber
authors.affiliation: CEA, LETI, DTBS, 17 Avenue des Martyrs, F-38054 Grenoble Cedex 9, France.
authors.forename: I
authors.initials: I
authors.lastname: Texier
authors.affiliation: INSERM U823, Institut Albert Bonniot, F-38 706 Grenoble, France; Université Joseph Fourier, F-38706 Grenoble, France.
authors.forename: J-L
authors.initials: JL
authors.lastname: Coll
authors.affiliation: LUNAM Université - Micro et Nanomédecines Biomimétiques, F-49933 Angers, France; INSERM U1066, IBS-CHU, 4 Rue Larrey, F-49933 Angers Cedex 9, France.
authors.forename: J-P
authors.initials: JP
authors.lastname: Benoit
authors.affiliation: LUNAM Université - Micro et Nanomédecines Biomimétiques, F-49933 Angers, France; INSERM U1066, IBS-CHU, 4 Rue Larrey, F-49933 Angers Cedex 9, France. Electronic address: Catherine.passirani@univ-angers.fr.
authors.forename: C
authors.initials: C
authors.lastname: Passirani
mesh_terms: D000818:Animals; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods*; D005456:Fluorescent Dyes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008055:Lipids / Q000737:chemistry*; D008819:Mice, Nude; D053769:Nanocapsules / Q000737:chemistry*; D061848:Optical Imaging / Q000379:methods*; D011092:Polyethylene Glycols / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D005456:Fluorescent Dyes; D008055:Lipids; D053769:Nanocapsules; D011092:Polyethylene Glycols
keywords: Biodistribution; Drug release; Encapsulation stability; Fluorescence imaging; Nanomedicine