title: Stealth nanocarriers based sterosomes using PEG post-insertion process.
abstract: Sterosomes (STEs), a new and promising non-phospholipidic liposome platform based on palmitic acid (PA) and cholesterol (Chol) mixtures, need to have polyethylene glycol (PEG) chains grafted to their surface in order to obtain long-circulating nanocarriers in the blood stream. A post-insertion method was chosen to achieve this modification. The post-insertion process of PEG-modified distearoylphosphoethanolamine (DSPE-PEG) was monitored using the zeta potential value of STEs. Various conditions including PEG chain length and the DSPE-PEG/PA-Chol ratio, were explored. Zeta potential of STEs changed from about -40mV for non-modified STEs to values close to 0mV by the end of the process, i.e. for PEG-modified STEs. The kinetics of DSPE-PEG insertion and the stability of the resulting PEG-modified STEs were not considerably influenced, within the investigated range, by changes in PEG chain lengths and in DSPE-PEG/PA-Chol proportion. The post-insertion of PEG chains reduced in vitro complement activation as well as in vitro macrophage uptake compared to the non-modified STEs. Moreover, longer blood circulation time in mice was established for PEG-modified STEs intravenously injected compared to non-modified STEs. These results establish that post-insertion process of PEG chains to STEs is a promising strategy for developing long-term circulating drug delivery nanocarriers.
authors.affiliation: MINT, UNIV Angers, INSERM 1066, CNRS 6021, Université Bretagne Loire, Angers, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Cieślak
authors.affiliation: MINT, UNIV Angers, INSERM 1066, CNRS 6021, Université Bretagne Loire, Angers, France; Laboratoire de Pharmacie Galénique et de Biopharmacie, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Wauthoz
authors.affiliation: MINT, UNIV Angers, INSERM 1066, CNRS 6021, Université Bretagne Loire, Angers, France.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Nieto Orellana
authors.affiliation: MINT, UNIV Angers, INSERM 1066, CNRS 6021, Université Bretagne Loire, Angers, France.
authors.forename: Nolwenn
authors.initials: N
authors.lastname: Lautram
authors.affiliation: MINT, UNIV Angers, INSERM 1066, CNRS 6021, Université Bretagne Loire, Angers, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Béjaud
authors.affiliation: MINT, UNIV Angers, INSERM 1066, CNRS 6021, Université Bretagne Loire, Angers, France; Pneumatology Department, Academic Hospital, Angers F-49933, France.
authors.forename: José
authors.initials: J
authors.lastname: Hureaux
authors.affiliation: Department of Chemistry, Université de Montréal, Montréal, QC, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Lafleur
authors.affiliation: MINT, UNIV Angers, INSERM 1066, CNRS 6021, Université Bretagne Loire, Angers, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Benoit
authors.affiliation: Iquir-Conicet, Facultad de Ciencias Bioquímicas y Farmacéuticas, Área Técnica Farmacéutica, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Claudio J
authors.initials: CJ
authors.lastname: Salomon
authors.affiliation: MINT, UNIV Angers, INSERM 1066, CNRS 6021, Université Bretagne Loire, Angers, France. Electronic address: guillaume.bastiat@univ-angers.fr.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bastiat
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000031:analogs & derivatives / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D005562:Formazans / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D053758:Nanoparticles / Q000737:chemistry*; D019308:Palmitic Acid / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: C488404:1,5-di(2-hydroxy-5-sulfophenyl)-3-cyanoformazan; D004337:Drug Carriers; D005562:Formazans; D008081:Liposomes; C118255:polyethylene glycol-cholesterol; D019308:Palmitic Acid; D011092:Polyethylene Glycols; D002784:Cholesterol
keywords: Biodistribution; CH50 experiment; Macrophage uptake; PEG; Sterosomes