title: Interfacial behavior of PEGylated lipids and their effect on the stability of squalenoyl-drug nanoassemblies.
abstract: Squalenoyl-gemcitabine (Sq-Gem) and squalenoyl-dideoxycytidine (Sq-ddC) are amphiphilic prodrugs that self-assemble in water to form nanoassemblies (NAs) with well-defined structures and size. However, like other drug nanocarriers, these nanoassemblies are rapidly cleared from the blood stream by the reticulo-endothelial system. By adding squalenoyl-PEG (Sq-PEG) or cholesterol-PEG (Chol-PEG) to the squalenoyl prodrugs, composite nanoassemblies (CNAs) were formed, with different sizes and structures. The effect of the PEG-lipids on the formation and stability of these nanoassemblies was assessed by transmission electron microscopy, quasi-elastic light scattering and surface tension measurements in various conditions. The results revealed different stabilities with time for Sq-ddC and Sq-Gem nanoassemblies in aqueous medium, the latter being much less stable than the former. They also demonstrated that the presence of Sq-PEG or Chol-PEG in composite Sq-ddC nanoassemblies contributed to their rapid destabilization. The analysis of the adsorption kinetics of Sq-PEG into a prodrug monolayer below and above its critical aggregation concentration allowed getting a better insight into prodrug-lipopolymer molecular interactions, and their consequences on the formation of composite prodrug nanoassemblies.
authors.affiliation: Univ Paris-Sud, IFR 141, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, 92296 Châtenay-Malabry Cedex, France; CNRS, UMR 8612, Institut Galien Paris-Sud, Châtenay-Malabry, France; Université Djillali Liabès de Sidi Bel Abbès, Faculté des Sciences, LCOPM, BP 89, Sidi Bel Abbès 22000, Algeria.
authors.forename: Fawzia
authors.initials: F
authors.lastname: Bekkara-Aounallah
authors.affiliation: Univ Paris-Sud, IFR 141, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, 92296 Châtenay-Malabry Cedex, France; CNRS, UMR 8612, Institut Galien Paris-Sud, Châtenay-Malabry, France.
authors.forename: Anshuman
authors.initials: A
authors.lastname: Ambike
authors.affiliation: Univ Paris-Sud, IFR 141, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, 92296 Châtenay-Malabry Cedex, France; CNRS, UMR 8612, Institut Galien Paris-Sud, Châtenay-Malabry, France.
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Gref
authors.affiliation: Univ Paris-Sud, IFR 141, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, 92296 Châtenay-Malabry Cedex, France; CNRS, UMR 8612, Institut Galien Paris-Sud, Châtenay-Malabry, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Couvreur
authors.affiliation: Univ Paris-Sud, IFR 141, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, 92296 Châtenay-Malabry Cedex, France; CNRS, UMR 8612, Institut Galien Paris-Sud, Châtenay-Malabry, France. Electronic address: veronique.rosilio@u-psud.fr.
authors.forename: Véronique
authors.initials: V
authors.lastname: Rosilio
mesh_terms: D000327:Adsorption; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000737:chemistry; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004355:Drug Stability; D057927:Hydrophobic and Hydrophilic Interactions; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry*; D013185:Squalene / Q000737:chemistry*; D013500:Surface Tension; D016047:Zalcitabine / Q000008:administration & dosage / Q000737:chemistry; D000093542:Gemcitabine
chemical_list: D004337:Drug Carriers; D011355:Prodrugs; C095164:poly(oxyethylene) cholesteryl ether; D003841:Deoxycytidine; D011092:Polyethylene Glycols; D016047:Zalcitabine; D013185:Squalene; D002784:Cholesterol; D000093542:Gemcitabine
keywords: Lipopolymer; Nanoassembly; Squalenic acid; Squalenoyl-dideoxycytidine; Squalenoyl-gemcitabine; Surface tension