title: Calorimetric study on pH-responsive block copolymer grafted lipid bilayers: rational design and development of liposomes.
abstract: This study is focused on chimeric advanced drug delivery nanosystems and specifically on pH-sensitive liposomes, combining lipids and pH-responsive amphiphilic block copolymers. Chimeric liposomes composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and two different forms of block copolymers, i.e. poly(n-butylacrylate)-b-poly(acrylic acid) (PnBA-b-PAA) at 70 and 85% content of PAA at six different molar ratios, each form respectively. PAA block exhibits pH-responsiveness, because of the regulative group of -COOH. -COOH is protonated under acidic pH (pKa ca. 4.2), while remains ionized under basic or neutral pH, leading to liposomes repulse and eventually stability. Lipid bilayers were prepared composed of DPPC and PnBA-b-PAA. Experiments were carried out using differential scanning calorimetry (DSC) in order to investigate their thermotropic properties. DSC indicated disappearance of pre-transition at all chimeric lipid bilayers and slight thermotropic changes of the main transition temperature. Chimeric liposomes have been prepared and their physicochemical characteristics have been explored by measuring the size, size distribution and ζ-potential, owned to the presence of pH-responsive polymer. At percentages containing medium to high amounts of the polymer, chimeric liposomes were found to retain their size during the stability studies. These results were well correlated with those indicated in the DSC measurements of lipid bilayers incorporating polymers in order to explain their physicochemical behavior. The incorporation of the appropriate amount of these novel pH-responsive block copolymers affects thus the cooperativity, the liposomal stabilization and imparts pH-responsiveness.
authors.affiliation: a Department of Pharmaceutical Technology, Faculty of Pharmacy , University of Athens , Panepistimioupolis , Zografou , Athens , Greece and.|b Theoretical and Physical Chemistry Institute, National Hellenic Research Foundation , Athens , Greece.
authors.forename: Natassa
authors.initials: N
authors.lastname: Pippa
authors.affiliation: a Department of Pharmaceutical Technology, Faculty of Pharmacy , University of Athens , Panepistimioupolis , Zografou , Athens , Greece and.
authors.forename: Maria
authors.initials: M
authors.lastname: Chountoulesi
authors.affiliation: a Department of Pharmaceutical Technology, Faculty of Pharmacy , University of Athens , Panepistimioupolis , Zografou , Athens , Greece and.
authors.forename: Aimilia
authors.initials: A
authors.lastname: Kyrili
authors.affiliation: b Theoretical and Physical Chemistry Institute, National Hellenic Research Foundation , Athens , Greece.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Meristoudi
authors.affiliation: b Theoretical and Physical Chemistry Institute, National Hellenic Research Foundation , Athens , Greece.
authors.forename: Stergios
authors.initials: S
authors.lastname: Pispas
authors.affiliation: a Department of Pharmaceutical Technology, Faculty of Pharmacy , University of Athens , Panepistimioupolis , Zografou , Athens , Greece and.
authors.forename: Costas
authors.initials: C
authors.lastname: Demetzos
mesh_terms: D002151:Calorimetry; D015195:Drug Design; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000138:chemical synthesis / Q000737:chemistry*; D015394:Molecular Structure; D011108:Polymers / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D008081:Liposomes; D011108:Polymers
keywords: Block copolymer; differential scanning calorimetry; drug delivery systems; lipids; pH-sensitive liposomes