• FARAH HAMAD FARAH Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman, United Arab Emirates


Objectives: This study aims to investigate the possible influence of the model, cationic, surface-active solute chlorpromazine hydrochloride (CPZ-HCl) on the size of small unilamellar dimyristoyl phosphatidylcholine (DMPC) liposomes as a function of temperature and CPZ-HCl concentration, below and above the critical micelle concentration (CMC).

Methods: Small unilamellar DMPC liposomes were prepared by dissolving DMPC in chloroform and the solvent was rota-evaporated in a water bath adjusted at 40 °C. The lipid film was then dispersed in 0.1 M KCl solution adjusted at pH 6.2 to form large multilamellar liposomes which are then sonicated and fractionated via Sepharose 2B-Cl gel. The elution profile was followed spectrophotometrically at λ 260 nm. Combined fractions from the trailing edge of the included peak which is due to small unilamellar liposomes, were used as a source throughout this study. The SOFICA light scattering photometer (Model 42000) was used to determine the weight average liposomes weight (Lw) of small unilamellar DMPC liposomes. The Lw was determined in the absence and presence of CPZ-HCl both above and below the CMC over the temperature range of 25 °C to 40 °C.

Results: The Lw was observed to increase linearly in the absence and presence of CPZ-HCl.

The Lw was observed to increase linearly in the absence of CPZ-HCl, from 1.88×106+0.02 g/mol at 25 °C to 3.25×106+0.03 g/mol at 40 °C. Similarly, the Lw was observed to increase linearly in the present of CPZ-HCl, for example at 18 mmol drug concentration, the Lw increases from 11×106+0.04 g/mol at 25 °C to 13.75×106+0.03 g/mol at 40 °C. When the data are presented as a function of CPZ-HCl concentration, a gradual increase in Lw was observed below the CMC. Little increase in Lw however, was observed at post-micellar concentrations of 14 mmol and 18 mmol.

Keywords: CPZ-HCl, DMPC liposome, Temperature, CMC


1. Akbarzadeh A, Rezaei Sadabady R, Davaran S, Joo SW, Zarghami N, Hanifehpour Y, et al. Liposome: classification, preparation, and applications. Nanoscale Res Lett 2013;8:102-11.
2. Gabizon A. Drug carrier systems. In: Roerdink FHD, Kron AM. editors. Liposomes as a drug delivery system in cancer therapy. First ed. Chichester: Wiley; 1989. p. 185–211.
3. A Storm G, Roerdink FH, Steerenberg PA, de Jong WH, Crommelin DJA. Influence of lipid composition on the antitumor activity exerted by doxorubicin-containing liposomes in a rat solid tumor model. Cancer Res 1987;47:3366–72.
4. Wiebe VJ, Degregorio MW. Liposome-encapsulated amphotericin-B: A promising new treatment for disseminated fungal infections. Rev Infect Dis 1988;19:1097-101.
5. Vogel NJ, Vogel CL, Henderson IC. The role of liposomal anthracyclines and other systemic therapies in the management of advanced breast cancer. Semin Oncol 2004;31;106-46.
6. Malam Y, Loizidou M, Seifalian AM. Liposomes and nanoparticles: nanosized vehicles for drug delivery in cancer. Trends Pharmacol Sci 2000;30:592-9.
7. Schurmann D, Dormann A, Grunewald T, Ruf B. Successful treatment of AIDS-related pulmonary Kaposi's sarcoma with liposomal daunorubicin. Eur Respir J 1994;7:824–5.
8. Sarvesh Sharma, Vimal Kumar. In vitro cytotoxicity effect on mcf-7cell line of co-encapsulated artesunate and curcumin liposome. Int J Pharm Pharm Sci 2016;8:286-92.
9. Razan Solayman Awad, Wassim Abdel Wahed, Yaser Bitar. Evaluating the impact of preparation conditions and formulation on the accelerated stability of tretinoin loaded liposomes prepared by the heating method. Int J Pharm Pharm Sci 2015;7:171-8.
10. Smita Bonde, Sukanya Nair. Advances in liposomal drug delivery system: Fascinating types and potential applications. Int J Appl Pharm 2017;9:1-7.
11. Claudia Zylberberg, Sandro Matosevic. Pharmaceutical liposomal drug delivery: a review of new delivery systems and a look at the regulatory landscape. Drug Delivery 2016;23:3319-29.
12. Giuseppina Bozzuto, Agnese Molinari. Liposomes as nanomedical devices. Int J Nanomed 2015;10:975–99.
13. Kuan Yi Lu, Sheng Ce Tao, Tzu Ching Yang,Yu Hsuan Ho, Chia Hsien Lee, Chen Ching Lin, et al. Profiling lipid-protein interactions using nonquenched fluorescent liposomal nanovesicles and proteome microarrays. Mol Cell Proteomics 2012;11:1177–90.
14. Antoaneta V Popova, Dirk K Hincha. Effects of cholesterol on dry bilayers: interactions between phosphatidylcholine unsaturation and glycolipid or free sugar. Biophys J 2007;93:1204–14.
15. Valeriya M Trusova, Galyna P Gorbenko, Julian G Molotkovsky, Paavo KJ Kinnunen. Cytochrome c-lipid interactions: new insights from resonance energy transfer. Biophys J 2010;99:1754–63.
16. El Maghraby GM, Williams AC, Barry BW. Drug interaction and location in liposomes: correlation with polar surface areas. Int J Pharm 2005;292:179-85.
17. Misagh Alipour, Zacharias E Suntres, Majed Halwani, Ali O Azghani, Abdelwahab Omri. Activity and interactions of liposomal antibiotics in presence of polyanions and sputum of patients with cystic fibrosis. PLoS One 2009;4:e5724.
18. Arrowsmith M, Hadgraft J, Kellaway IW. The interaction of cortisone esters with liposomes as studied by differential scanning calorimetry. Int J Pharm 1983;16:305-18.
19. Hiroko Osanai, Tastuya Ikehara, Seiji Miyauchi, Kazumi Shimono, Jun Tamogami, Toshifumi Nara, et al. A study of the interaction of drugs with liposomes with isothermal titration calorimetry. J Biophysical Chem 2013;4:11-21.
20. Isabel D Alves, Galya Staneva, Cedric Tessier, Gilmar F Salgadod, Philippe Nuss. The interaction of antipsychotic drugs with lipids and subsequent lipid reorganization investigated using biophysical methods. Biochim Biophys Acta 2011;1808:2009-18.
21. Ahmed M, Hadgraft J, Burton JS, Kellaway IW. The interaction of mequitazine with phospholipid model membranes. Chem Phys Lipid 1980;27:251-62.
22. Anteneodo C, Bisch PM, Marques JF. Interaction of chlorpromazine with phospholipid membranes: an EPR study of membrane surface potential effects. Eur Biophys J 1995;23:447-52.
23. Willy Nerdal, Stig Are Gundersen, Vidar Thorsen, Harald Høiland, Holm Holmsen. Chlorpromazine interaction with glycerophospholipid liposomes studied by magic angle spinning solid state 13C-NMR and differential scanning calorimetry. Biochim Biophys Acta Biomembr 2000;1464:165-75.
24. Breton J, Viret J, Leterrier F. Calcium and chlorpromazine interactions in rat synaptic plasma membranes: A spin-label and fluorescence probe study. Arch Biochim Biophys 1977;179:625-33.
25. Song Chen, Anja Underhaug Gjerde, Holm Holmsen, Willy Nerdal. Importance of polyunsaturated acyl chains in chlorpromazine interaction with phosphatidylserines: a 13C and 31P solid-state NMR study. Biophysical Chem 2005;117:101-9.
26. Plantavid M, Chap H, Lloveras J, Douste Blazy L. Cationic amphiphilic drugs as potential tools for modifying phospholipid of tumor cells: an in vitro study of chlorpromazine effects on krebs II ascites cells. Biochem Pharmac 1981;30:293-7.
27. Seeman F, Kwant WO, Sauks T, Argent W. Membrane expansion of erythrocyte ghosts by tranquilizers and anesthetics. Biochem Biophys Acta 1969;183:499-511.
28. Szoka FJ, Papahadjopoulos D. Comparative properties and methods of preparation of lipid vesicles (liposomes). Ann Rev Biophys Bioeng 1980;9:467-508.
29. Richardson VJ, Jeyasingh K, Jewkes RF, Ryman BE, Tattersall MHN. Possible tumor localization of Tc-99-m-labeled liposomes: effects of lipid composition, charge and liposome size. J Nucl Med 1978;19:1049-54.
30. Libusa Sikurova, M Kristekova. Fluorescence anisotropy and light-scattering studies of the interaction of insulin with liposomes. J Fluorescence 1993;3:215-7.
31. Duke RW, Dupre DB. Inelastic light scattering at the second critical micellar formation of lecithin. Chem Phys Lett 1976;44:309-12.
32. Kellaway IW, Saunders L. Osmotic pressure studies of some phospholipid sols. Chem Phys Lipid 1970;4:261-8.
33. Baxa U. Imaging of liposomes by transmission electron microscopy. Methods Mol Biol 2018;1682:73-88.
34. Del Amo EM, Rimpelä AK, Heikkinen E, Kari OK, Ramsay E, Lajunen T, et al. Pharmacokinetic aspects of retinal drug delivery. Prog Retin Eye Res 2017;57:134-85.
35. Mason JT, Huang C. Hydrodynamic analysis of egg phosphatidylcholine vesicles. Ann N Y Acad Sci 1978;308:29-49.
36. London E, Feigenson GW. A convenient and sensitive fluorescence assay for phospholipid vesicles using diphenylhexatriene. Anal Biochem 1978;88:203-11.
37. Larrabee AL. Time dependent changes in the size distribution of distearoylphosphatidylcholine vesicles. Biochemistry 1979;18:3321-6.
38. Padday JE, Russel DR. The measurement of the surface tension of pure liquids and solutions. J Colloid Sci 1960;15:503-11.
39. Riddick JA, Bunger WB. Organic solvents; techniques of chemistry. Vol. II. 3rd ed. New York: Wiley interscience; 1970.
40. Zimm BH. The scattering of light and the radial distribution function of high polymer solutions. J Chem Phys 1984;16:1093-100.
41. Beattie WH, Booth C. Table of dis-symmetries and correction factors for use in light scattering. J Phys Chem 1964;64:696-7.
42. Pugh WJ, Saunders L. A laser light scattering apparatus. J Pharm Pharmacol 1971;23 Suppl 1:85-8.
43. Huglin MB. Light scattering from polymer solutions. 3rd ed. New York: Academic Press; 1972.
44. Beckett AH, Stenlake JB. Practical pharmaceutical chemistry. Part 2. 3rd ed. The Athlone Press of the University of London; 1976.
45. Farah FH. Micro-electrophoretic mobility study of the Influence of chlorpromazine hydrochloride on dimyrstoyl-phosphatidylcholine liposomes in different media. Int J Pharm Sci Res 2015;6:3245-53.
46. Watts A, Marsh D, Knowles PF. Characterization of DMPC vesicles and their dimensional changes through the phase transition-molecular control of membrane morphology. Biochemistry 1978;17:1792-801.
47. Kwant WO, Steveninck JV. The influence of chlorpromazine On human erythrocytes. Biochem Pharmacol 1986;17:2215-23.
48. Green AL. Ionization constants and water solubilities of some amino-alkyl-phenothiazine tranquilizers and related compounds. J Pharm Pharmac 1967;19:10-6.
49. Lee AG. Local anesthesia: the interaction between phospholipids and chlorpromazine, propranolol and practolol. Mol Pharma 1977;13:474-87.
50. Nussio Matthew R, Sykes Matthew J, Miners John O, Shapter Joseph G. Characterisation of chlorpromazine binding to lipid bilayer membranes. International Conference on Nanoscience and Nanotechnology; 2006. ICONN.2006.340603.
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