Mechanism of Antidepressant Drug Loading in Surface-Active Ionic Liquid: Insights from Micelle Morphology and Energy Analysis Using Coarse-Grained MD Simulations

Poor water solubility of many active pharmaceutical ingredients limits their bioavailability and therapeutic efficacy. Surface-active ionic liquids (SAILs), with their tunable physicochemical properties and strong self-aggregation behavior, offer a promising strategy for drug delivery by forming mixed assemblies with drug molecules that influence micellar structure, morphology, and interactions. In the current study, a coarse-grained molecular dynamics (CG) simulation was carried out to investigate the mechanism of loading of an antidepressant drug, imipramine (IMP), with 1-decyl-3-methylimidazolium bromide (DMI) in aqueous medium at a concentration range. Mixing soluble DMI surface-active ionic liquids with hydrophobic IMP drugs modulates the encapsulation of drug molecules by influencing aggregation behavior. The molar fraction determined the loading and distribution of imipramine in mixed micelles. Due to the synergistic interaction from the incorporation of IMP among DMI monomers, larger and more compact mixed micelles with higher aggregation numbers were formed. At lower concentrations, IMP monomers capture inside DMI micelles, while, at higher concentrations, they self-assemble alongside DMI molecules. The IMP weakens the electrostatic repulsive interaction between DMI monomers. The strong synergistic interactions between the SAIL and drug molecules in the mixed micelles are attributed to the formation of cationic mixtures.