Chlorpromazine interaction with glycerophospholipid liposomes studied by magic angle spinning solid state C-13-NMR and differential scanning calorimetry

Phosphatidylserine (PS) extracted from pig brain and synthetic dipalmitoylp hosphatidylcholine (DPPC) and dimyristoylphosphatidylcholine (DMPC) were us ed to make DPPC/DMPC and DPPC/PS large unilamellar liposomes with a diamete r of similar to 1 mu m Chlorpromazine-HCl (CPZ), an amphipathic cationic ps ychotropic drug of the phenothiazine group, is known to partition into lipi d bilayer membranes of liposomes with partition coefficients depending on t he acyl chain length and to alter the bilayer structure in a manner dependi ng on the phospholipid headgroups. The effects of adding CPZ to these membr anes were studied by differential scanning calorimetry and proton cross pol arization solid state magic angle spinning C-13-nuclear magnetic resonance spectroscopy (CP-MAS-C-13-NMR). CP-MAS-C-13-NMR spectra of the DPPC (60%)/D MPC (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 densel y packed bilayer. Conversely, the DPPC (54%)/PS (36%)/CPZ (10%) bilayer at 25 degrees C demonstrates interaction of CPZ with the phospholipid headgrou ps (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 c hains 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), sh ows CPZ interdigitation among the phospholipids as deduced from the finding that similar to 30% of the phospholipid acyl chains carbon resonances shif t low-field by 5-15 ppm. (C) 2000 Published by Elsevier Science B.V. All ri ghts reserved.