Cubic-to-inverted micellar and the cubic-to-hexagonal-to-micellar transitions on phytantriol-based cubosomes induced by solvents.

Abstract

Cubosomes are nanoparticles composed of a specific combination of some types of amphiphilic molecules like lipids, such as phytantriol (PHY), and a nonionic polymer, like poloxamer (F127). Cubosomes have a high hydrophobic volume (>50%) and are good candidates for drug delivery systems. Due totheir unique structure, these nanoparticles possess the ability to incorporate highly hydrophobic drugs. A challenge for the encapsulation of hydrophobic molecules is the use of organic solvents in the sample preparation process. In this study, we investigated the structural influence of four different solvents (acetone, ethanol, chloroform, and octane), by means of small-angle X-ray scattering and cryogenic electron microscopy techniques. Inthe presence of ahigh amount of acetone and ethanol (1:5 solvent:PHY volumetric ratio), for instance, a cubic-to-micellar phase transition was observed due to the high presence of these two solvents. Chloroform and octane have different effects over PHY-based cubosomes as compared to acetone and ethanol, both of them induced a cubic-to-inversehexagonal phase transition. Thoseeffects are attributed to the insertion of the solvent in the hydrophobic region of the cubosomes, increasing itsvolume and inducing such transition. Moreover, a second phase transition from reversed hexagonal-to-inverted micellar was observed for chloroform and octane. The data also suggest that after 24h of solvent/cubosome incubation, some structural features of cubosomes change as compared to the freshly prepared samples. This study could shed light on drug delivery systems using PHY-based cubosomes to choose the appropriate solvent in orderto load the drug into the cubosome.Graphical abstract.