The Effects of a Tranquilizer on Lipid Bilayers.
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The interactions between the amphiphilic drug, chlorpromazine hydrochloride (CPZ) and phospholipid systems that are common in the cell membrane, specifically dipalmitoylphosphatidylcholine (DPPC), were studied using <sup>31</sup>P nuclear magnetic resonance spectroscopy (NMR), differential scanning calorimetry (DSC), and isothermal titration calorimetry (ITC).NMR and DSC results showed that the size of the lipid bilayer affected the incorporation of the drug into the bilayer.CPZ incorporated into the bilayer more readily in extruded unilamellar 1000 ? diameter vesicles than in multilayers.The solvents used were also found to influence the mixing of CPZ and DPPC.In addition, CPZ and DPPC were studied over a wide range of temperatures via titration calorimetry.Using extruded unilamellar lipid vesicles and phosphate buffer as solvent, the ITC results showed that the thermodynamics on the interactions between CPZ and DPPC were temperature dependent. At 46 <sup>o</sup>C, the heats were observed in the range of ?1200uJ and 10,000uJ.The interaction was exothermic when CPZ/DPPC mole ratio, X, = 0.06 to X = 0.08 and became endothermic at X = 0.08 to X = 0.12 mole ratio.These experiments were also performed at 37 <sup>o</sup>C and 30 <sup>o</sup>C.