Niosomes are versatile nanocarriers for therapeutic compounds, and optimizing their structures via ionic surfactants can enhance their functionality considerably. Catanionic niosomes, which have the capability of both cationic and anionic niosomes, are attractive vehicles for drug delivery objectives. Here, we aim to design and evaluate catanionic niosome as a vehicle for anticancer agents.

A molecular modeling pipeline was performed to model the physicochemical properties of cationic, anionic, and catanionic niosomes as a multifunctional drug delivery system for Cabozantinib. SPAN60 was used as the nonionic surfactant, cholesterol was the stabilizer, DOTAP and DCP were used as the cationic and anionic surfactants, respectively, and cabozantinib, an FDA-approved c-Met inhibitor was chosen as the drug compound. Some meaningful parameters relevant to the cabozantinib molecule and its characteristics in the bilayer, such as hydrogen bonding, total energy, the radius of gyration (Rgyr), mean square displacements (MSD), diffusion coefficient, and the radial distribution function (RDF) were evaluated and compared between the formulations.

The outcomes revealed that hydrogen bonding of cabozantinib is more probable with DOTAP, and the total energy of the drug is lower in anionic formulation (-180 kcal/mol). The MSD showed that cationic niosome restricts the movement of cabozantinib, while the drug could be efficiently released from the anionic niosome, and catanionic niosome can equilibrate the movement of the drug with a diffusion coefficient of 5.73 × 10⁻¹² (m²/s).

This technique could effectively describe the behavior of drugs in various bilayer compositions, and the catanionic niosomes are potential multifunctional carriers for anticancer agents.