In this manuscript, we identify the underlying molecular scale mechanisms that drive the solubilisation of two different small molecule drugs within Triton X-114 surfactant micelles, and how the solubilisation affects the structural properties of the micelles. Specifically, we have investigated the solubilisation of the sodium salts of two different nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen and indomethacin. While the structural properties of Triton X-114 micelles have been studied with both experimental and simulation approaches, very little has been done to investigate its properties as a potential drug delivery vehicle. In this work, we have used all-atom molecular dynamics simulations to characterise the structure of ibuprofen and indomethacin-loaded Triton X-114 micelles, and obtain a detailed understanding of how the aggregation mechanisms of the drug molecules affect the structure of these micelles.
The results of our work shows that as the Triton X-114 micelle solubilises drug molecules it becomes more non-spherical, with the ibuprofen-loaded micelle becoming more non-spherical than the indomethacin-loaded micelle. We find that at saturation conditions approximately twice as much indomethacin is loaded into the core of the micelle than ibuprofen. We also find that the indomethacin molecules form larger aggregates within the core of the micelle than ibuprofen. The growth of these larger aggregates in the indomethacin-loaded micelle results in the destabilisation of the micelle core. This leads to the indomethacin-loaded micelle dividing into two daughter micelles, which are different in size. This insight into how the interactions of drug micelles drive the change in structure and stability of a micelle have important ramifications for the rational design of new drug delivery vehicles in the future.
Full reference: NSAID solubilisation promotes morphological transitions in Triton X-114 surfactant micelles. Hrachya Ishkhanyan, Robert M. Ziolek, David J. Barlow, M. Jayne Lawrence, Armen H. Poghosyan & Christian D. Lorenz, Journal of Molecular Liquids (2022) 356, 119050.