Synchrotron SAXS and WAXS Study of the Interactions of NSAIDs with Lipid Membranes

Abstract

Cell membranes often constitute the first biological structure encountered by drugs, and binding or interactions of drugs with lipid components of the membrane may explain part of their mechanism of activity or their side effects. The present study provides evidence of alterations in the structural properties of phospholipid bilayers at acidic conditions that can be correlated with the mechanism of action of nonsteroidal anti-inflammatory drugs (NSAIDs) and with their local action effect on the gastrointestinal tract lipids, aiming a molecular biophysical approach to the interaction of these drugs with lipid membranes. In this context, the structural modifications of the 1,2-dipalmitoyl-sn-glycero-3-phosphocholine bilayers at pH 5.0, induced by increasing concentrations of five NSAIDs (piroxicam, meloxicam, tolmetin, indomethacin, and nimesulide), were studied by small-angle and wide-angle X-ray scattering. Results obtained highlight the effect of each NSAID in modulating the membrane structure properties. All the NSAIDs promoted distinct biophysical effects by perturbing the membrane arrangement to different degrees that are intimately related to their different physicochemical properties as well as with the initial organization of the lipids, depending if they are in the gel (Lβˈ) or in the liquid-crystalline phase (Lα).

Structural properties of paeonol encapsulated liposomes at physiological temperature: Synchrotron small-angle and wide-angle X-ray diffraction studies

“…As shown in the table, in the absence of sterols and drugs, the d-spacing of SAXS and WAXS of pure DPPC liposomes at 37°C are 7.02 nm and 0.423 nm, respectively. These data are in good agreement with other studies and represent a typical lamellar-gel phase [20,22,35]. …”

“…Nunes et al reported that a reduction of the correlation length of the SAXS induced by adding exogenous molecules could manifest the disturbing effect of exogenous molecules in the membrane order [19,20]. As shown in Table 1, all the correlation lengths (ξ ) of SAXS of sterol-DPPC liposomes encapsulating paeonol are shorter than that of sterol-DPPC liposomes in the absence of paeonol.…”

“…Then d (d = 1/s) was calculated. The diffraction peaks obtained was fitted with Lorentz [2,19,20], and the full widths at half maximal intensity (FWHM) were determined. The correlation length (ξ ) between the lipid bilayers, was calculated following [2,19,20] …”

Evaluation of the Structure–Activity Relationship of Rifabutin and Analogs: A Drug–Membrane Study

“…[21] The effect of the antimycobacterial compounds on the structure of EPC:-CHOL (4:1) bilayer was investigated by small-angle X-ray scattering (SAXS). [22] The results presented herein, besides unraveling the mechanism by which these antimycobacterial compounds diffuse across the membranes, demonstrate that the interactions of the antimycobacterial compounds with the membranes are dependent on small changes in their chemical structure. Additionally, a possible relationship between the modifications in the lead structure and the effects on the membranes was established, which allows prediction of their putative bioavailability and toxic effects.…”

“…The diffraction peaks were fitted with Lorentzians and the positions of the maximum intensities and the full-widths of the peaks at halfheight were determined. [22] …”