title: Chlorpromazine interaction with glycerophospholipid liposomes studied by magic angle spinning solid state (13)C-NMR and differential scanning calorimetry.
abstract: Phosphatidylserine (PS) extracted from pig brain and synthetic dipalmitoylphosphatidylcholine (DPPC) and dimyristoylphosphatidylcholine (DMPC) were used to make DPPC/DMPC and DPPC/PS large unilamellar liposomes with a diameter of approximately 1 microm. Chlorpromazine-HCl (CPZ), an amphipathic cationic psychotropic drug of the phenothiazine group, is known to partition into lipid bilayer membranes of liposomes with partition coefficients depending on the acyl chain length and to alter the bilayer structure in a manner depending on the phospholipid headgroups. The effects of adding CPZ to these membranes were studied by differential scanning calorimetry and proton cross polarization solid state magic angle spinning (13)C-nuclear magnetic resonance spectroscopy (CP-MAS-(13)C-NMR). CP-MAS-(13)C-NMR spectra of the DPPC (60%)/DMPC (40%) and the DPPC (54%)/DMPC (36%)/CPZ (10%) liposomes, show that CPZ has low or no interaction with the phospholipids of this neutral and densely packed bilayer. Conversely, the DPPC (54%)/PS (36%)/CPZ (10%) bilayer at 25 degrees C demonstrates interaction of CPZ with the phospholipid headgroups (PS). This CPZ interaction causes about 30% of the acyl chains to enter the gauche conformation with low or no CPZ interdigitation among the acyl chains at this temperature (25 degrees C). The DPPC (54%)/PS (36%)/CPZ (10%) bilayer at a sample temperature of 37 degrees C (T(C)=31.2 degrees C), shows CPZ interdigitation among the phospholipids as deduced from the finding that approximately 30% of the phospholipid acyl chains carbon resonances shift low-field by 5-15 ppm.
authors.affiliation: Department of Chemistry, University of, Allegaten 41, N-5007, Bergen, Norway.
authors.forename: W
authors.initials: W
authors.lastname: Nerdal
authors.forename: S A
authors.initials: SA
authors.lastname: Gundersen
authors.forename: V
authors.initials: V
authors.lastname: Thorsen
authors.forename: H
authors.initials: H
authors.lastname: Høiland
authors.forename: H
authors.initials: H
authors.lastname: Holmsen
mesh_terms: D002152:Calorimetry, Differential Scanning; D002247:Carbon Isotopes; D002746:Chlorpromazine / Q000737:chemistry*; D020404:Glycerophospholipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D013696:Temperature
chemical_list: D002247:Carbon Isotopes; D020404:Glycerophospholipids; D008081:Liposomes; D002746:Chlorpromazine