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

Abstract

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.

Comprehensive NMR Investigation of Imidazolium-Based Ionic Liquids [BMIM][OSU] and [BMIM][Cl] Impact on Binding and Dynamics of the Anticancer Drug Doxorubicin Hydrochloride

“…The molecular structure of DOX, IL1, and IL2 are listed in Figure 1. 13 C chemical shift perturbations of a surfactant/micelle in the presence of additives, such as drug, 29 polymer, 43,44 etc., when compared against an additive-free situation can provide the information on site-specific binding and the underlying microstructure. In this regard, 13 C NMR spectra were recorded for the mixtures D and E (aqueous IL controls) with assignments (Figure S2A,B) considered based on the earlier reports.…”

“…To throw further light on the local environment of the drug−IL complex relative to the IL-free situation, activation energies were extracted from the temperature dependence of translational dynamics. 29 The activation energies (E a s) of DOX were extracted by fitting the D DOX data against temperature (Figure 3) modeled by the equation D = D o e −Ea/RT . From the observed slopes of Arrhenius plots (ln D vs 1000/T), the E a s of DOX were noted to be 29.3 ± 2.5, 24.7 ± 1.9, and 33.3 ± 1.3 kJ/mol in mixture-A, mixture-B, and mixture-C, respectively (Figure 3).…”

“…39 Of late, a detailed NMR study of DOX with SDS micelle by employing 13 C chemical shifts, 2 H spin relaxation, 1 H diffusometry, 1D transient and steady-state NOE, and 2D NOESY was reported elsewhere. 29 The DOX complexation with submicellar [C 8 MIM] [Cl] in terms of large vesicular aggregates was characterized by scattering and imaging techniques. 3 Nevertheless, a molecular/atomic level understanding of imidazolium-based ILs with DOX employing NMR is still scanty.…”

“…The former is known as the greener IL over the latter. 40 Furthermore, our recent NMR results on DOX with membrane mimic SDS 29 prompted us to investigate the subtle details involved in DOX with the above-chosen IL surfactant monomers. It may be noted that earlier NMR reports on drug interaction were focused on surfactant micelles composed of SDS 33 and DDAC, 34 whereas in the present work surfactant (IL) monomers are used to induce complexation with DOX.…”

Transparent Superhydrophobic Coatings of Silica Nanoparticles Using Functionalized Polyurethanes

“…NMR spin-lattice relaxation time (T 1 ) is sensitive to fast motions alone, while spin-spin relaxation time (T 2 ) invites the contributions from slow and fast motions. [30] Hence, in the present context, the relaxation rate difference ~R (= 1/T 2 -1/T 1 ) provides fruitful information on slow dynamics [31] due to binding of polymer with silica nanoparticles. The interaction between the functionalized polymer (PPU1) and silica nanoparticles (D-g-SiO 2 ) were studied using both T 1 and T 2 .…”