In this work, we elucidate the underlying molecular scale mechanisms which drive the encapsulation of two different small molecule drugs within Triton X-100 surfactant micelles, and how the encapsulation effects the structural properties of the micelles. Specifically, we have investigated the encapsulation of two different nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen and indomethacin. While the structural properties of Triton X-100 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 a combination of small angle neutron scattering and all-atom molecular dynamics simulations to characterise the structure of ibuprofen and indomethacin loaded Triton X-100 micelles, and obtain a detailed understanding of how the aggregation mechanisms of the drug molecules affects the structure of these micelles.
The results of our work shows that as the Triton X-100 micelle encapsulates drug molecules it becomes more non-spherical, and the ibuprofen-loaded micelle is more non-spherical than the indomethacin-loaded micelle. We investigated the molecular mechanisms that result from the encapsulation of the two drugs. We find that at saturation conditions approximately twice as much indomethacin is loaded into the core of the micelle than ibuprofen. Also we find that the indomethacin molecules form larger aggregates within the core of the micelle than ibuprofen. The growth of these larger aggregates results in the indomethacin-loaded micelle results in the destabilisation of the micelle core, which results in more water entering into the core of the micelle. These two mechanisms then lead to the indomethacin-loaded micelle dividing into two daughter micelles. This insight into how the interactions of drug micelles drive the change in structure and stability of a micelle could be quite important in future design of drug delivery vehicles.
Full reference: Impact of drug aggregation on the structural and dynamic properties of Triton X-100 micelles. Hrachya Ishkhanyan, Natasha H. Rhys, David Barlow, M. Jayne Lawrence & Christian D. Lorenz, Nanoscale (2022) 14, 5392-5403.