NSAID solubilisation promotes morphological transitions in Triton X-114 surfactant micelles

The structural properties of micelles formed by the non-ionic surfactant, Triton X-114 (TX-114), were investigated using all-atom molecular dynamics (MD) simulations. Additionally, we investigated the effect of the solubilisation of the sodium salts of two nonsteroidal anti-inflammatory drugs, ibuprofen and indomethacin, upon the structural properties of TX-114 micelles. The micelle in absence of the drugs has an aspherical shape. We find that as the micelle continues to solubilise drug molecules, its shape becomes even more elongated. The solubilised drug molecules are observed to take orientations within the core of the micelle that allows their carboxyl groups to remain hydrated by the surrounding interfacial solvent. Also we find that the increased aggregation of indomethacin via π-π stacking of its chlorobenzene group leads to destabilisation of the micelle. In the ibuprofen-loaded micelle, where the solubilised drug molecules do not aggregate to the same degree, we find that the drug-loaded micelle remains stable. These results provide a mechanistic description of how the solubilisation of NSAIDs drives morphological changes in TX-114 micelles. Additionally, we show how the physico-chemical properties of both surfactants and drug molecules can play a significant role in the stabilisation of drug delivery vehicles.