Cubosomes as Versatile Multifunctional Lipid-Based Nanocarriers for Drug Delivery: A Comprehensive Review.

Abstract

Cubosomes (QBS) are self-assembled, nanostructured lipid carriers characterized by a bicontinuous cubic liquid crystalline architecture with a three-dimensional honeycomb-like morphology. Their unique internal structure allows simultaneous encapsulation of hydrophilic, lipophilic, and amphiphilic compounds, enabling sustained, site-specific, and targeted drug delivery through various routes, including oral, ocular, nasal, transdermal, and vaginal administration. Composed primarily of amphiphilic lipids such as Glyceryl Monooleate (GMO) and stabilized with surfactants like Pluronic F-127, QBS exhibits superior biocompatibility, structural integrity, and long-term colloidal stability. QBS are typically fabricated using either top-down or bottom-up strategies. Top-down approaches such as high-pressure homogenization, probe sonication, and spray drying fragment bulk cubic phases into nanosized dispersions, ensuring scalability and uniformity. Conversely, bottom-up methods, including the hydrotrope technique, vortex dispersion, and solvent evaporation, enable spontaneous QBS formation under mild conditions ideal for thermolabile actives. Physicochemical properties depend on lipid-to-stabilizer ratios, solvent composition, and processing parameters. Characterization techniques such as Dynamic Light Scattering (DLS), Small-Angle X-ray Scattering (SAXS), Transmission Electron Microscopy (TEM), and Confocal Laser Scanning Microscopy (CLSM) confirm particle size, morphology, and internal nanostructure. Zeta potential and MTT assays evaluate stability and cytocompatibility, while in vitro and ex vivo studies assess drug entrapment, release, and permeation behaviour. QBS represent an advanced class of lyotropic liquid-crystalline nanocarriers with high drug-loading potential, excellent biocompatibility, and controlled-release performance. Their multifunctional versatility underscores their promise as next-generation platforms for targeted and sustained drug delivery applications.