Molecular Dynamics Study of Catanionic Bilayers Composed of Ion Pair Amphiphile with Double-Tailed Cationic Surfactant An-Tsung Kuo, †,‡ Chien-Hsiang Chang, † and Wataru Shinoda* ,‡ † Department of Chemical Engineering, National Cheng Kung University, Tainan 701, Taiwan ‡ Nanosystem Research Institute (NRI), National Institute of Advanced Industrial Science and Technology (AIST), Central-2, Umezono 1-1-1, Tsukuba 305-8568, Japan * S Supporting Information ABSTRACT: The physical stability of catanionic vesicles is important for the development of novel drug or DNA carriers. For investigating the mechanism by which catanionic vesicles are stabilized, molecular dynamics (MD) simulation is an attractive approach that provides microscopic structural information on the vesicular bilayer. In this study, MD simulation was applied to investigate the bilayer properties of catanionic vesicles composed of an ion pair amphiphile (IPA), hexadecyltrimethylammonium- dodecylsulfate (HTMA-DS), and a double-tailed cationic surfactant, ditetradecyldimethylammonium chloride (DTDAC). Structural information regarding membrane elasticity and the organization and conformation of surfactant molecules was obtained based on the resulting trajectory. Simulation results showed that a proper amount of DTDAC could be used to complement the asymmetric structure between HTMA and DS, resulting in an ordered hydrocarbon chain packing within the rigid membrane observed in the mixed HTMA-DS/DTDAC system. The coexistence of gel and fluid phases was also observed in the presence of excess DTDAC. MD simulation results agreed well with results obtained from experimental studies examining mixed HTMA-DS/DTDAB vesicles. 1. INTRODUCTION Recently, the number of studies examining vesicles has increased because of their potential as drug delivery carriers. Vesicles composed of lipid are called liposomes, which have a similar composition to cell membranes. Liposomes are relatively nontoxic and can be decomposed in vivo. Therefore, they are widely used as carriers for drug delivery. 1,2 Addition- ally, it is relatively easy to modify the liposomal surface with targeting ligands or antibodies, which can further reduce side effects and improve drug efficacy. 3 Thus, vesicles have been widely studied. 1,4-7 However, the practical application of liposomes appears to be limited due to high costs. To solve this problem, catanionic vesicles prepared from inexpensive catanionic surfactants have recently been considered as a feasible replacement with significant potential to serve as novel drug or DNA carriers. 8-11 Catanionic surfactants are defined as mixtures of cationic and anionic surfactants. After removing counterions from the mixtures, the catanionic surfactant residue is referred to as ion pair amphiphile (IPA). 8 It has been reported that catanionic vesicles prepared from IPAs are not stable. 12,13 Physical stability of catanionic vesicles can be improved using additives that increase electrostatic and/or steric repulsion between vesicles or that modify molecular packing or intermolecular interaction within vesicles. 14-19 However, mechanisms for stabilizing catanionic vesicles prepared using mixtures of IPAs and additives remain unclear at the molecular level. MD simulations may be useful for investigating the microscopic structure of vesicular bilayers. A large number of MD studies examining lipid bilayers using fully atomistic as well as coarse-grained descriptions have been reported. 20-29 These MD studies have provided insight into bilayer structural and elastic properties such as lipid conformation, elastic modulus, and density profiles, 22,25-27 improving the understanding of lipid bilayers from a molecular viewpoint. Catanionic vesicles prepared from hexadecyltrimethylammo- nium-dodecylsulfate (HTMA-DS) showed poor physical stability, and a double-chained cationic surfactant, ditetrade- cyldimethylammonium bromide (DTDAB), was shown to be efficient in enhancing the stability of vesicles. 30 However, the mechanism underlying this increase in vesicle stability is not understood. In order to explore the physical properties of catanionic vesicles composed of HTMA-DS and DTDAB, a series of MD simulations of bilayers with several different compositions of HTMA-DS and DTDAB (DTDAC, ditetra- decyldimethylammonium chloride, was used in this study) were conducted. Structural properties, together with the membrane area elastic modulus, were analyzed. The effect of composition Received: February 14, 2012 Revised: April 13, 2012 Published: May 7, 2012 Article pubs.acs.org/Langmuir © 2012 American Chemical Society 8156 dx.doi.org/10.1021/la300651u | Langmuir 2012, 28, 8156-8164