Oleoylethanolamide-Based Lyotropic Liquid Crystals as Vehicles for Delivery of Amino Acids in Aqueous Environment

We have investigated the phase behavior of self-assembled lyotropic liquid crystals (LC) formed by ternary mixtures of oleoylethanolamide (OEA), water and arginine. OEA, a natural analog of the endogenous cannabinoid anandamide involved in the peripheral regulation of feeding, was selected as a main component due to its capacity to induce efficient decreases in food intake and gains in body mass. Arginine was selected as representative hydrophilic amino acid and added to the OEA-water mixture at different concentrations. The phase diagrams were determined by combining cross-polarized optical microscopy and small angle x-ray scattering. First, the phase diagram for the OEA-water system was determined. It was shown that these two compounds give rise to reverse la3d double gyroid and reverse Pn3m double diamond cubic phases existing in bulk over a large window of temperature and composition, and that for water content beyond 25% Pn3m coexisted with excess water. Successively, the influence of arginine as guest molecule in the water channels of the reverse LC was investigated. For the sake of comparison, results for the OEA-water-arginine system were compared with analog series of OEA-water-glucose. The results showed that, at a fixed water content and temperature, the phase behavior of the liquid crystalline phases is strongly dependent on arginine concentration. In more detail, arginine could be encapsulated in the bulk OEA-water LC up to 2.0% wt, whereas transitions from la3d to Pn3m cubic phase were observed with increasing arginine concentration. Interestingly, upon an increase of water concentration beyond 20-25%, Pn3m phase started to coexist with excess water releasing the arginine in external water solution. Quantitative measurements of arginine content inside the LC water channels and in the excess external water solution revealed a complete release of the amino acid, demonstrating that the investigated lyotropic liquid crystalline systems can be used as ideal vehicles for the delivery of functional hydrophilic active molecules in aqueous environment.