ABSTRACT
Abstract: Cubosomes are nanostructured lipid-based particles that have gained significant attention in the field of drug delivery and nanomedicine. These unique structures consist of a three-dimensional cubic lattice formed by the self-assembly of lipid molecules. The lipids used to construct cubosomes are typically nonionic surfactants, such as monoolein, which possess both hydrophilic and hydrophobic regions, allowing them to form stable, water-dispersible nanoparticles. One of the key advantages of cubosomes is their ability to encapsulate and deliver hydrophobic as well as hydrophilic drugs. The hydrophobic regions of the lipid bilayers provide an ideal environment for incorporating lipophilic drugs, while the hydrophilic regions can encapsulate water-soluble drugs. This versatility makes cubosomes suitable for delivering a wide range of therapeutic agents, including small molecules, proteins, peptides, and nucleic acids. The unique structure of cubosomes also offers stability and controlled release benefits. The lipid bilayers provide a protective barrier, shielding the encapsulated drugs from degradation and improving their stability. Moreover, the cubic lattice arrangement enables the modulation of drug release kinetics by varying the lipid composition and surface modifications. This allows for the development of sustained or triggered drug release systems, enhancing therapeutic efficacy and reducing side effects. Furthermore, cubosomes can be easily modified with targeting ligands or surface modifications to achieve site-specific drug delivery, enhancing therapeutic selectivity and reducing off-target effects. In conclusion, cubosomes offer a versatile and promising platform for the delivery of therapeutic agents. In this manuscript, we will highlight some of these applications.
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 to their 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. In the presence of a high 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-inverse hexagonal phase transition. Those effects are attributed to the insertion of the solvent in the hydrophobic region of the cubosomes, increasing its volume 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 24 h 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 order to load the drug into the cubosome.Graphical abstract.
