Preparation of Cubosomes with Improved Colloidal and Structural Stability Using a Gemini Surfactant

Abstract

Cubosomes are nanoparticles with bicontinuous cubic internal nanostructures that have been considered for use in drug delivery systems (DDS). However, their low structural stability is a crucial concern for medical applications. Herein, we investigated the use of a gemini surfactant, sodium dilauramidoglutamide lysine (DLGL), which is composed of two monomeric surfactants linked with a spacer to improve the structural stability of cubosomes prepared with phytantriol (PHY). Uniform nanosuspensions comprising a specific mixing ratio of DLGL and PHY in water prepared via ultrasonication were confirmed by using dynamic light scattering. Small-angle X-ray scattering and cryo-transmission electron microscopy revealed the formation of Pn 3̅ m cubosomes in a range of DLGL/PHY solid ratios between 1 and 3% w/w. By contrast, cubosome formation was not observed at DLGL/PHY solid ratios of 5% w/w or higher, suggesting that excess DLGL interfered with cubosome formation and caused them to transform into small unilamellar vesicles. The addition of phosphate-buffered saline to the nanosuspension caused aggregation when the solid ratio of DLGL/PHY was less than 5% w/w. However, Im 3̅ m cubosomes were obtained at solid ratios of DLGL/PHY of 6, 7.5, and 10% w/w. The lattice parameters of the Pn 3̅ m and Im 3̅ m cubosomes were approximately 7 and 11–13 nm, respectively. The lattice parameters of Im 3̅ m cubosomes were affected by the concentration of DLGL. Pn 3̅ m cubosomes were surprisingly stable for 4 weeks at both 25 and 5 °C. In conclusion, DLGL, a gemini surfactant, was found to act as a new stabilizer for PHY cubosomes at specific concentrations. Cubosomes composed of DLGL are stable under low-temperature storage conditions, such as in refrigerators, making them a viable option for heat-sensitive DDS.

Recent Advances in the Use of Cubosomes as Drug Carriers with Special Emphasis on Topical Applications

“…A further increase in concentration > 5% or 6% w/w disrupts the formation of CBs and transforms them into small unilamellar vesicles. The prepared samples were found to be stable at a 2% DLGL/PHY concentration, confirming the adequate concentration to form stable Im3m cubic structures [ 84 ].…”