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Preparation of Cubosomes with Improved Colloidal and Structural Stability Using a Gemini Surfactant.
Masao Nagao1,2, Abdul-Hackam Ranneh3, Yasunori Iwao4
1Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
Molecular Pharmaceutics
|September 19, 2023
Summary
Gemini surfactant sodium dilauramidoglutamide lysine (DLGL) enhances phytantriol (PHY) cubosome stability for drug delivery systems (DDS). DLGL-stabilized cubosomes show promise for heat-sensitive pharmaceuticals requiring refrigerated storage.
Area of Science:
- Nanotechnology and Materials Science
- Pharmaceutical Sciences and Drug Delivery
Background:
- Cubosomes, nanoparticles with bicontinuous cubic structures, are promising for drug delivery systems (DDS).
- A key limitation for cubosomes in medical applications is their insufficient structural stability.
- Gemini surfactants, like sodium dilauramidoglutamide lysine (DLGL), offer potential for stabilizing nanostructures.
Purpose of the Study:
- To investigate the stabilization of phytantriol (PHY)-based cubosomes using the gemini surfactant DLGL.
- To determine the optimal concentrations and conditions for DLGL-PHY cubosome formation and stability.
- To evaluate the potential of DLGL-stabilized cubosomes for drug delivery applications, particularly for heat-sensitive materials.
Main Methods:
- Preparation of cubosome nanosuspensions using specific mixing ratios of DLGL and PHY in water via ultrasonication.
- Characterization of cubosome structure and morphology using dynamic light scattering (DLS), small-angle X-ray scattering (SAXS), and cryo-transmission electron microscopy (cryo-TEM).
- Assessment of cubosome stability upon addition of phosphate-buffered saline (PBS) and under different temperature storage conditions (5 °C and 25 °C).
Main Results:
- Formation of Pn3̅m cubosomes was confirmed at DLGL/PHY solid ratios between 1-3% w/w, with lattice parameters around 7 nm.
- At higher DLGL/PHY ratios (≥5% w/w), cubosome formation was inhibited, leading to small unilamellar vesicles; however, Im3̅m cubosomes formed at 6-10% w/w.
- Pn3̅m cubosomes exhibited remarkable stability for 4 weeks at both 5 °C and 25 °C, indicating suitability for refrigerated storage.
Conclusions:
- Sodium dilauramidoglutamide lysine (DLGL) effectively stabilizes phytantriol (PHY) cubosomes at specific concentrations, acting as a novel stabilizer.
- DLGL-stabilized cubosomes demonstrate excellent structural integrity under low-temperature storage, crucial for heat-sensitive drug delivery applications.
- These findings highlight DLGL-based cubosomes as a viable and stable platform for advanced drug delivery systems.
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