Insight into molecular structures and dynamical properties of niosome bilayers containing melatonin molecules: a molecular dynamics simulation approach

Niosomes represent vesicular carriers capable of encapsulating both hydrophobic and hydrophilic drugs within their inner core or bilayer shell. They are typically composed of non-ionic synthetic surfactants such as sorbitan monostearate (Span60) with the addition of cholesterol (Chol). The physical properties and stability of niosomal vesicles strongly depend on the composition of their bilayers, which plays a significant role in determining the efficiency of drug encapsulation and release in drug delivery systems. In this study, we have explored the interactions between melatonin (Mel) molecules and the niosome bilayer, as well as their resulting physical properties. Molecular dynamics simulations were employed to investigate melatonin-inserted niosome bilayers, both with and without the inclusion of cholesterol. The simulation results revealed that cholesterol notably influences the location of melatonin molecules within the niosome bilayers. In the absence of cholesterol, melatonin tends to occupy the region around the Span60 tail groups. However, in the presence of cholesterol, melatonin is found in the vicinity of the Span60 head groups. Melatonin molecules in niosome bilayers without cholesterol exhibit a more ordered orientation when compared to those in bilayers containing 50 mol% cholesterol. The bilayer structure of the Span60/Mel and Span60/Chol/Mel systems exhibited a liquid-disordered phase (Ld). In contrast, the Span60/Chol bilayer system displays a liquid-ordered phase (Lo) with less fluidity. This study reveals that melatonin induces a disorderly bilayer structure and greater lateral expansion, whereas cholesterol induces an orderly bilayer structure and a more condensed effect. Cholesterol plays a crucial role in condensing the bilayer structure with stronger interactions between Span60 and cholesterol. The addition of 50 mol% cholesterol in the Span60 bilayers not only enhances the stability and rigidity of niosomes but also facilitates the easier release of melatonin from the bilayer membranes. This finding is particularly valuable in the context of preparing niosomes for drug delivery systems. The niosome bilayer containing melatonin exhibits the liquid-disordered phase, resulting in increased fluidity. Furthermore, the inclusion of 50 mol% cholesterol in the bilayer enhances melatonin mobility in both lateral and transverse directions.