The membrane-activity of Ibuprofen, Diclofenac, and Naproxen: A physico-chemical study with lecithin phospholipids

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) represent non-specific inhibitors of the cycloxygenase pathway of inflammation, and therefore an understanding of the interaction process of the drugs with membrane phospholipids is of high relevance. We have studied the interaction of the NSAIDs with phospholipid membranes made from dimyristoylphosphatidylcholine (DMPC) by applying Fourier-transform infrared spectroscopy (FTIR), Förster resonance energy transfer spectroscopy (FRET), differential scanning calorimetry (DSC) and isothermal titration calorimetry (ITC). FTIR data obtained via attenuated total reflectance (ATR) show that the interaction between DMPC and NSAIDs is limited to a strong interaction of the drugs with the phosphate region of the lipid head group. The FTIR transmission data furthermore are indicative of a strong effect of the drugs on the hydrocarbon chains inducing a reduction of the chain-chain interactions, i.e., a fluidization effect. Parallel to this, from the DSC data beside the decrease of T(m) a reduction of the peak height of the melting endotherm connected with its broadening is observed, but leaving the overall phase transition enthalpy constant. Additionally, phase separation is observed, inducing the formation of a NSAID-rich and a NSAID-poor phase. This is especially pronounced for Diclofenac. Despite the strong influence of the drugs on the acyl chain moiety, FRET data do not reveal any evidence for drug incorporation into the lipid matrix, and ITC measurements performed do not exhibit any heat production due to drug binding. This implies that the interaction process is governed by only entropic reactions at the lipid/water interface.

The interaction of cannabinoid receptor agonists, CP55940 and WIN55212-2 with membranes using solid state 2H NMR

“…This effect, frequently found for many anesthetics [34–36], has also been observed with other cannabinoids [4,37]. Additionally, the phase transition of the phospholipid bilayer accompanying reduction in temperature is significantly ligand dependent.…”

Interaction of O-acylated chitosans with biomembrane models: Probing the effects from hydrophobic interactions and hydrogen bonding

“…6C. Such shifts could be explained by dehydration of the P O groups owing to incorporation of DACT and DPPCT, according to Moreno et al [42] that attributed to hydration a shift to smaller wavenumbers owing to incorporation of nonsteroidal antiinflammatory drugs in phospholipid monolayers. These results can be compared with the effects from parent chitosan on DMPA monolayers [23], where chitosan was found to promote ordering in the DMPA chains and hydration in the headgroup, with the P O stretching band being shifted to lower wavenumbers.…”

Amorphous drug dispersions with mono- and diacyl lecithin: On molecular categorization of their feasibility and UV dissolution imaging

“…In such rather ordered systems, the phospholipid geometry has been demonstrated to impact on drug solubilization in liposomal bilayers (Ali et al, 2013). Hydrated phospholipids would lead with ionizable NSAIDs to an interaction on the lipid/ water interface that is greatly governed by entropy contribution to the binding free energy (Moreno et al, 2009). Thus, drug interaction with the phospholipid in an anhydrous solid matrix must be viewed as a clearly separate case compared to hydrated phospholipids, which is in agreement with the findings of Huesch et al (2011).…”