Effects of a cationic surfactant incorporation in phytantriol bulk cubic phases and dispersions loaded with the anticancer drug 5-fluorouracil

Ordered lyotropic liquid crystalline phases, which are particularly interesting for several biological and biomedical applications, can show the advantage of having a tunable three-dimensional nanostructure. Addition of ionic surfactants to lipid/water binary systems may influence their phase behavior and their structural properties, such as bilayer thickness, water channel diameter and interfacial curvature, resulting in specific amphiphile self-assembly materials. Understanding the effects of such additives is thus of considerable interest and, in this context, we studied the incorporation of a cationic surfactant (didodecyldimethylammonium bromide) in the phytantriol cubic phase, unloaded and loaded with the anticancer drug 5-fluorouracil. In particular, an anionic form of the drug was also used which could further influence the mesophase structure of the lipid matrix and its entrapment efficiency. The formulations, prepared as bulk and dispersed phases, were characterized by synchrotron small angle X-ray scattering, attenuated total reflection Fourier transform infrared and UV–Vis spectroscopies and dynamic light scattering. Addition of increasing amounts of the cationic surfactant resulted in phase changes following the sequence Pn3m-Im3m-Lα, which was almost unaltered when the drug in its neutral form was encapsulated in the systems. On the contrary, the presence of the anionic 5-fluorouracil stabilized the Pn3m cubic phase at all the cationic surfactant concentrations used.