Molecular Packing and Lateral Interactions of Distearoylphosphatidylcholine with Dihexadecyldimethylammonium Bromide in Langmuir Monolayers and Vesicles Chien-Hsiang Chang, † Chia-Hua Liang, ‡ Yu-Ying Hsieh, † and Tzung-Han Chou* ,§ § Department of Chemical and Materials Engineering, National Yunlin University of Science and Technology, Yunlin 64002, Taiwan † Department of Chemical Engineering, National Cheng Kung University, Tainan 701, Taiwan ‡ Department of Cosmetic Science, Chia Nan University of Pharmacy and Science, Tainan 717, Taiwan ABSTRACT: The behavior of distearoylphosphatidylcholine (DSPC) mixed with dihexadecyldimethylammonium bromide (DHDAB) in the monolayer was investigated by means of Langmuir trough, interfacial thermodynamic analysis, and Brewster angle microscopy. It was found that the cationic surfactant, DHDAB, was miscible with DSPC and a condensing effect, indicating stronger contraction of area per molecule and stronger ordering molecular packing, appeared in the mixed DSPC/DHDAB monolayers. Condensed structures of the mixed monolayers were visible as the molar fraction of DHDAB (X DHDAB ) ≤ 0.7. The negative deviations of excess area and mixing Gibbs free energy were obtained, and their minimum values occurred at X DHDAB = 0.3, suggesting that a DSPC/DHDAB monolayer with this composition exhibited the most pronounced intermolecular interactions with a compact molecular arrangement than the monolayers with separation between individual components. Furthermore, characteristics of mixed DSPC/DHDAB vesicles dispersed in water were studied by dynamic light scattering, transmission electron microscopy, and fluorescence polarization. The DSPC vesicles added with DHDAB showed zeta potentials of about +50 mV and narrower size distributions than those of pure DSPC vesicles. DSPC formed more rigid membranes than DHDAB, and the minimum disordering effect on membrane packing of vesicles was found at X DHDAB = 0.5, which was the most stable vesicle composition against aggregation. By contrast, the condensing effect and the increase of intermolecular attraction in mixed DSPC/DHDAB monolayers may be related to the stability enhancement of mixed vesicles as compared with the stability of pure component vesicles. ■ INTRODUCTION In the past two decades, cationic vesicles have caused great interest not only because of their capacity for drug delivery but also due to their utilization as a nonviral carrier for gene transfection. 1-3 It is now widely recognized that vesicles composed of cationic surfactants with neutral phosphatidylcho- lines can successfully deliver negatively charged DNA into cells through electrostatic interactions. 4 Nevertheless, cationic vesicles designed for DNA delivery usually exhibit low physical stability and undergo structural changes as interacting with cells. 5,6 Most cationic surfactants for gene delivery system are toxic and have been reviewed by Lv et al. 7 However, it has been found that the cytotoxicity of cationic surfactants in vesicles can be reduced by adding phosphatidylcholines. 8 Cytotoxicity, gene transfection performance, and colloidal stability of these cationic vesicles are related closely to the vesicular constituents. Thus, finding out an optimal vesicular membrane composition of phosphatidylcholine/cationic surfactants for DNA delivery still deserves considerable attention. 9,10 The commonly utilized zwitterionic lipids for preparation of cationic liposomes are phosphatidylcholines or phosphatidyle- thanolamines and are able to increase efficiency of gene transfection with reduced cytotoxicity. 1,11 Additionally, syn- thetic cationic surfactants, dialkyldimethylammonium bro- mides, have been increasingly utilized due to their cationic phospholipid-like structure, low cost, and specific medically efficacy. 12-14 Recently, the dispersion behavior of binary dipalmitoylphosphatidylcholine (DPPC)/dioctadecyldimethy- lammonium bromide (DODAB) vesicles formed by a simple vortex approach has been examined by size distribution, zeta potential, turbidity, and fluorescence polarization measure- ments. 15 It has been revealed that the vesicle size decreased but zeta potential remained constant with increasing the DODAB mol %, and the maximum phase transition temperature (T m ) and colloidal stability were obtained at a composition of 50 mol % DODAB. 15 The previous report by Linseisen et al. 16 has also mentioned that DPPC vesicles containing 50 mol % DODAB expressed higher T m than vesicles composed of each pure component. Montalvo et al. 17 have found that only mixing lecithin/didodecyldimethylammonium bromide (DDAB) in water could form lamellar vesicles, and their structures and viscoelastic behavior depended on the composition. Therefore, Received: November 22, 2011 Revised: January 20, 2012 Published: February 2, 2012 Article pubs.acs.org/JPCB © 2012 American Chemical Society 2455 dx.doi.org/10.1021/jp211264h | J. Phys. Chem. B 2012, 116, 2455-2463