NMR Studies on the Interaction of Anticancer Drug Doxorubicin with Membrane Mimetic SDS

In the formulation of efficient drug delivery systems, it is essential to unravel the structural and dynamical aspects of the drug's interaction with biological membranes. This has been done for the anticancer drug-membrane system comprising doxorubicin hydrochloride (DOX), a water-soluble anticancer drug, and the micellar sodium dodecyl sulfate (SDS), the latter serving as a useful mimic for membrane proteins. Using a multimodal NMR approach involving ¹H, ²H, and ¹³C as probe nuclei and through the determination of chemical shifts, spin-relaxation, nuclear Overhauser enhancements (NOE), and translational self-diffusion (SD), the binding characteristics of the DOX with SDS have been determined. The perturbation to ¹³C chemical shifts of SDS indicate the penetration of DOX into the SDS micelle, which is further revealed by ¹H-¹H NOESY and SD measurements. ²H spin-relaxation measurements and their analysis using a two-step model show DOX induced SDS micellar volume changes, which determine the correlation times involved in the DOX-SDS mobility.