Formulating stable hexosome dispersions with a technical grade diglycerol-based surfactant

We report on the phase behavior of a technical grade and commercially available diglycerol monoisostearate, C41V, and its use for the preparation of nanostructured liquid crystal dispersions (hexosomes). C41V in water forms a reverse hexagonal liquid crystal at room temperature and in a wide range of concentrations (0.5–95 wt%); this hexagonal liquid crystal is stable up to 70 °C. A simple and effective method has been developed to disperse hexosomes with an encapsulated active molecule (Ketoprofen) that consists of (1) producing a nano-emulsion stabilized by an amphiphilic block copolymer (Pluronic F127) and containing ethyl acetate and C41V by using ultrasounds and (2) evaporating the solvent to produce hexosomes. The size of the hexosomes and ultrasound dispersion time is markedly reduced by using ethyl acetate as an auxiliary solvent with an optimal initial ratio of C41V:ethyl acetate of 50:50. Dynamic light scattering shows that the size of the hexosomes decreases as the concentration of stabilizer F127 or encapsulated Ketoprofen is increased. The lattice parameter in the hexagonal structure is calculated from small angle scattering data to be ca. 5.3 nm and is only slightly dependent on the amount of F127 and/or encapsulated Ketoprofen. Cryo electron microscopy reveals that the samples contain hexosomes and these coexist with spherical, likely F127 micelles. Lastly, hexosomes show a pH responsive release of Ketoprofen which could be useful for target delivery in the gastrointestinal tract. © 2019 Elsevier Inc.Financial support from the Ministry of Science, Innovation and Universities (grant CTQ2017-84998-P ) and Spanish National Research Council (CSIC) (grant I-LINK 1188) is gratefully acknowledged. Synchrotron SAXS experiments were performed at BL11-NCD beamline at ALBA Synchrotron Light Facility with the collaboration of ALBA staff. DLS measurements have been performed at the Nanostructured Liquid Characterization Unit, located at the Institute of Advanced Chemistry of Catalonia (IQAC), belonging to the Spanish National Research Council (CSIC) and affiliated to the NANBIOSIS ICTS of the Biomedical Networking Research Center (CIBER-BBN). Appendix APeer reviewe