Niosomes are vesicular liposomes prepared from nonionic surfactants such as Span, Tween, and Brij. With a good chemical stability and low cost of production, they were originally developed to substitute phospholipid vesicles in drug delivery. Due to a higher transdermal permeability and penetrability, niosomes have attracted much interest in the research field of topical drug delivery. There have been numerous reports on the application of niosomes in the transdermal delivery of various drugs.1 Properties such as entrapment efficiency and release rate have also been studied extensively.2 However, detailed structural studies are scarce and thus the physicochemical properties of niosomes are not readily explained at the atomic level. In this respect a theoretical modeling such as molecular dynamics (MD) simulation can provide a structural basis for the interpretation of experimental results.3 To our knowledge this is the first report on MD simulation of a niosomal bilayer of any kind.The structures and atom numbering of sorbitan monooleate (Span 80) and cholesterol are shown in Figure 1. The Gromos 43a1-s3 force field 4 was used in the calculation because it has been extended to include several phospholipids and cholesterol. Topology and parameters for the oleate and glycerol fragments of Span 80 were transferred from 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). Parameters for sorbitan moiety were obtained from those of similar structures listed in the Gromos 43a1-s3 force filed. A monolayer was constructed by filling 144 Span 80 molecules into a 12 × 12 array of equally sized boxes. A 8 × 8 array (total 64 molecules) was used for DOPC. Random rotation of the molecule within a grid did not alter the final simulation suggesting that the results were independent of the initial structures. The layer was duplicated and inverted to make a bilayer. Packmol, 5 a free software useful for the construction of a solvated bilayer, was used to fill water molecules below and above the bilayer at a thickness of 1.5 nm and density of 10 3 kg/m 3 . The resulting structure was subjected to an energy minimization and subsequently equilibrated for 100 ps at 1 bar and 298 K. A production MD simulation was carried out for 60 ns and the final 20 ns trace was used in the analysis of various physical properties. Particle mesh Ewald method 6 was used in the calculation of Coulomb interactions. Cutoff values for the Coulomb and van der Waals interactions were 1.0 and 1.6 nm, respectively. Bond lengths were constrained by using the LINCS algorithm 7 to allow a 2 fs integration. The temperature of