title: Impact of interfacial cholesterol-anchored polyethylene glycol on sterol-rich non-phospholipid liposomes.
abstract: OBJECTIVE
  Liposomes made of single-chain amphiphiles and a large amount of sterols display several advantages including a limited permeability. In the present paper, we examine the possibility to prepare such non-phospholipid liposomes with interfacial polyethylene glycol (PEG) in order to improve their circulation in the blood stream. Cholesterol (Chol) was chosen as the PEG anchor.
  
  
  METHODS
  The phase behavior of mixtures of palmitic acid (PA) and cholesterol including various proportions of PEGylated cholesterol (PEG-Chol) was characterized. In conditions leading to the formation of fluid bilayers, properties of the resulting liposomes were assessed.
  
  
  RESULTS
  Up to 20 mol% of PEGylated cholesterol could be introduced without significant perturbations in fluid bilayers made of PA and cholesterol. With 10 mol% PEG-Chol, PA/Chol/PEG-Chol liposomes showed a very limited permeability to calcein and doxorubicin. Doxorubicin could be actively loaded in PA/Chol/PEG-Chol liposomes with a high drug loading efficiency and a high drug to lipid ratio. Pharmaco-kinetic experiments in rats indicated that interfacial PEG reduced the clearance of PA/Chol liposomes compared to the naked ones. However the lifetime of these non-phospholipid liposomes in the blood circulation was considerably shorter than that observed for control PEGylated phospholipid liposomes, a phenomenon associated with the negative interfacial charge of the PA/Chol/PEG-Chol liposomes.
authors.affiliation: Department of Chemistry, Centre for Self-Assembled Chemical Structures (CSACS), Université de Montréal, C.P. 6128, Succ. Centre Ville, Montréal, Québec H3C 3J7, Canada. Electronic address: zhongkai.cui@umontreal.ca.
authors.forename: Zhong-Kai
authors.initials: ZK
authors.lastname: Cui
authors.affiliation: Department of Chemistry - BMC, Uppsala University, Box 579, SE 751 23 Uppsala, Sweden. Electronic address: katarina.edwards@kemi.uu.se.
authors.forename: Katarina
authors.initials: K
authors.lastname: Edwards
authors.affiliation: INSERM U1066, Micro et Nanomédecines Biomimétiques-MINT, Angers F-49933, France; LUNAM Université, UMR-S1066, Angers F-49933, France. Electronic address: a.otein.o@gmail.com.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Nieto Orellana
authors.affiliation: INSERM U1066, Micro et Nanomédecines Biomimétiques-MINT, Angers F-49933, France; LUNAM Université, UMR-S1066, Angers F-49933, France. Electronic address: guillaume.bastiat@univ-angers.fr.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bastiat
authors.affiliation: INSERM U1066, Micro et Nanomédecines Biomimétiques-MINT, Angers F-49933, France; LUNAM Université, UMR-S1066, Angers F-49933, France. Electronic address: jean-pierre.benoit@univ-angers.fr.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Benoit
authors.affiliation: Department of Chemistry, Centre for Self-Assembled Chemical Structures (CSACS), Université de Montréal, C.P. 6128, Succ. Centre Ville, Montréal, Québec H3C 3J7, Canada. Electronic address: michel.lafleur@umontreal.ca.
authors.forename: Michel
authors.initials: M
authors.lastname: Lafleur
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000097:blood; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000097:blood; D008081:Liposomes / Q000097:blood / Q000737:chemistry*; D019308:Palmitic Acid / Q000097:blood / Q000737:chemistry*; D010539:Permeability; D011092:Polyethylene Glycols / Q000737:chemistry*; D017207:Rats, Sprague-Dawley
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; C118255:polyethylene glycol-cholesterol; D019308:Palmitic Acid; D011092:Polyethylene Glycols; D004317:Doxorubicin; D002784:Cholesterol
keywords: Active loading; Cholesterol; Liposomes; Nanovectors; Palmitic acid; Permeability; Pharmaco-kinetics; Polyethylene glycol