The interactions between drugs and cell membranes can modulate the structural and physical properties of membranes. The resultant perturbations of the membrane integrity may affect the conformation of the proteins inserted within the membrane, disturbing the membrane-hosted biological functions. In this study, the droplet interface bilayer (DIB), a model cell membrane, is used to examine the effects of ibuprofen, a nonsteroidal antiinflammatory drug (NSAID), on transbilayer water permeability, which is a fundamental membrane biophysical property. Our results indicate that the presence of neutral ibuprofen (pH 3) increases the water permeability of the lipid membranes composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). When cholesterol is present with the DOPC, however, the water permeability is not influenced by addition of ibuprofen, regardless of the cholesterol content in DOPC. Given the fact that cholesterol is generally considered to impact packing in the hydrocarbon chain regions, our findings suggest that a potential competition between opposing effects of ibuprofen molecules and cholesterol on the hydrocarbon core environment of the phospholipid assembly may influence the overall water transport phenomena. Results from confocal Raman microspectroscopy and interfacial tensiometry show that ibuprofen molecules induce substantial structural and dynamic changes in the DOPC lipid bilayer. These results, demonstrating that the presence of ibuprofen increases the water permeability of pure DOPC but not that of DOPC−cholesterol mixtures, provide insight into the differential effect of a representative NSAID on heterogeneous biological membranes, depending upon the local composition and structure, results which will signal increased understanding of the gastrointestinal damage and toxicity induced by these molecules.
Cannabidiol (CBD), the major nonpsychoactive component of plant-derived cannabinoids, has been reported to have a broad range of potential beneficial pharmacological effects on the central nervous system (CNS). In this study, the droplet interface bilayer, a model cell membrane, is used to examine the effects of CBD on passive water permeability, a fundamental membrane biophysical property. The presence of CBD decreases the water permeability of model lipid membranes composed of 1,2dioleoyl-sn-glycero-3-phosphocholine (DOPC) and at low concentrations of cholesterol (Chol) (20 mol %) in DOPC, whereas when higher concentrations of Chol are present (33 mol %), CBD has an opposing effect, increasing water permeability. The diametric effect in water permeability change upon addition of CBD to Chol-low and Chol-high bilayers signifies a variant interaction of CBD, depending on the initial state of bilayer packing and fluidity. Additionally, differential scanning calorimetry studies provide evidence that there are selective changes in thermotropic behavior for CBD with DOPC and with DOPC/Chol membranes, respectively, supportive of these varying membrane interactions of CBD dependent upon cholesterol. The intriguing ability of CBD to sensitively respond to membrane Chol concentrations in modifying physical properties highlights the significant impact that CBD can have on heterogeneous biomembranes including those of the CNS, the neurons of which are enriched in Chol to a point where up to a quarter of the body's total Chol is in the brain, and defective brain Chol homeostasis is implicated in neurodegenerative diseases.
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