Enhanced loading of water-soluble actives into bicontinuous cubic phase liquid crystals using cationic surfactants

Over the past few years, bicontinuous cubic phase liquid crystals have been investigated for their applicability to controlled delivery of active ingredients. These liquid crystals have a unique structure of interpenetrating channels of water and lipid that provides compatibility with water-soluble, lipid-soluble, and amphiphilic active ingredients. Actives tend to be stable in the matrix and the structure provides control over their release. However, loading of water-soluble actives is difficult. It is especially problematic for cubic phase liquid crystal dispersions (cubosomes) given the large fraction of bulk water present. The inherent problem reflects the preference of the water-soluble actives to associate with water rather than with the liquid crystals. Ideally, the properties of the liquid crystal can be tailored to enhance the association of the liquid crystal with the active, thereby increasing loading. It is found that the inclusion of surfactant into the liquid crystal can provide this function. This work illustrates the enhanced loading of negatively charged, water-soluble active ketoprofen by the inclusion of positively charged surfactants into the liquid crystal. Loading differences resulting from the inclusion of dioctadecyl dimethyl ammonium chloride (DODMAC) and dioctadecyl ammonium chloride (DOAC) into the liquid crystal demonstrate that the magnitude of the enhancement is dependent on the surfactant concentration and the steric nature of its head group. The upper limit of the enhancement is explored by the inclusion of di(canola ethyl ester) dimethyl ammonium chloride (DEEDAC) formulated to greater than 20 wt% and demonstrates an order-of-magnitude enhancement over previous reports. This work provides a practical demonstration of functionalizing cubic phase liquid crystals and lays the framework for future work. (C) 2003 Elsevier Science (USA). All rights reserved.