NMR Approaches to Study Drug-Surfactant Interactions: Insights From NOE, Relaxometry and Diffusometry

Characterising drug-binding mechanisms, structural changes and dynamics at atomic resolution remains a challenge due to the dynamic and heterogeneous nature of surfactant supramolecular assemblies. In this context, nuclear magnetic resonance (NMR) is uniquely suited to overcome these complexities by offering precise information on binding, structure, dynamics and transport in native-like conditions. NMR spectroscopy, leveraging the nuclear Overhauser effect (NOE), spin-relaxometry and translational self-diffusometry, offers atomistic-level insights into drug-surfactant interactions. NOE measurements reveal spatial proximities between drug and surfactant molecules, while relaxometry captures local dynamics and facilitates the estimation of rotational correlation times for both free and bound drug species. Diffusometry probes global translational motion and geometric features, enabling quantification of the bound drug fraction (p_b) and partition coefficient (K), both of which are pertinent to pharmaceutical and chromatographic contexts. Together, these NMR approaches provide an integrated view of structure, dynamics and transport, which is critical for understanding the physicochemical behaviour of drug-surfactant systems. This mini-review summarizes key solution-state NMR techniques, supported by theoretical models and selected applications, for incisive characterisation of these interactions.