curcumin and 1-2-oleoylphosphatidylcholine

Curcumin is a hydrophobic drug gaining growing attention because of its high availability, its innocuity, and its anticancer, antitumoral, and antioxidative activity. However, its poor ‎‎bioavailability in the human body, caused by its low aqueous solubility and fast degradation, ‎‎presents a big hurdle for its oral administration. Here, we used nano-vesicles made of ‎‎phospholipids to carry and protect curcumin in its membrane. Various curcumin amounts were ‎‎encapsulated in the produced phospholipid system to form drug-loaded liposomes. ‎Curcumin's ‎concentration was evaluated using UV-visible measurements. The maximal ‎amount of curcumin ‎that could be added to liposomes was assessed. Nuclear magnetic ‎resonance (NMR) analyses ‎were used to determine curcumin's interactions and localization ‎within the phospholipid ‎membrane of the liposomes. X-ray scattering (SAXS) and atomic ‎force microscopy (AFM) ‎experiments were performed to characterize the membrane structure ‎and organization, as well as its ‎mechanical properties at the nanoscale. Conservation of the membrane's properties is found with ‎the addition of curcumin in various ‎amounts before saturation, allowing the preparation of a ‎defined nanocarrier with desired ‎amounts of the drug.

Topics: Antineoplastic Agents, Phytogenic; Curcumin; Drug Compounding; Drug Delivery Systems; Liposomes; Phosphatidylcholines; Solutions; Water

The cell membrane is an ordered environment, which anisotropically affects the structure and interactions of all of its molecules. Monitoring membrane orientation at a local level is rather challenging but could reward crucial information on protein conformation and interactions in the lipid bilayer. We monitored local lipid ordering changes upon varying the cholesterol concentration using polarized light spectroscopy and pyrene as a membrane probe. Pyrene, with a shape intermediate between a disc and a rod, can detect microscopic orientation variations at the level of its size. The global membrane orientation was determined using curcumin, a probe with nonoverlapping absorption relative to that of pyrene. While the macroscopic orientation of a liquid-phase bilayer decreases with increasing cholesterol concentration, the local orientation is improved. Pyrene is found to be sensitive to the local effects induced by cholesterol and temperature on the bilayer. Disentangling local and global orientation effects in membranes could provide new insights into functionally significant interactions of membrane proteins.

Topics: Cholesterol; Curcumin; Light; Lipid Bilayers; Liposomes; Molecular Probes; Phosphatidylcholines; Pyrenes; Spectrum Analysis

Curcumin, a dietary polyphenol, is a natural spice with preventive and therapeutic potential for neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Curcumin possesses a spectrum of antioxidant, anti-inflammatory, anticarcinogenic, and antimutagenic properties. Because of this broad spectrum of pharmacological activity, it has been suggested that, like cholesterol, curcumin exerts its effect on a rather basic biological level, such as on lipid bilayers of biomembranes. The effect of curcumin on translational mobility of lipids in biomembranes has not yet been studied. In this work, we used (1)H NMR diffusometry to explore lateral diffusion in planar-oriented bilayers of dimyristoylphosphatidylcholine (DMPC) and dioleoylphosphatidylcholine (DOPC) at curcumin concentrations of up to 40 mol % and in the temperature range of 298-333 K. The presence of curcumin at much lower concentrations (∼7 mol %) leads to a decrease in the lateral diffusion coefficient of DOPC by a factor of 1.3 at lower temperatures and by a factor of 1.14 at higher temperatures. For DMPC, the diffusion coefficient decreases by a factor of 1.5 at lower temperatures and by a factor of 1.2 at higher temperatures. Further increasing the curcumin concentration has no effect. Comparison with cholesterol showed that curcumin and cholesterol influence lateral diffusion of lipids differently. The effect of curcumin is determined by its solubility in lipid bilayers, which is as low as 10 mol % that is much less than that of cholesteroĺs 66 mol %.

Topics: Cholesterol; Curcumin; Dimyristoylphosphatidylcholine; Lipid Bilayers; Phosphatidylcholines; Temperature

The lipid matrix, or the lipid bilayer, of cell membranes is a natural binding site for amphipathic molecules, including antimicrobial peptides, pore-forming proteins, and many drugs. The unique property of pore-forming antimicrobial peptides is that they exhibit a threshold concentration (called the lethal concentration or the minimum inhibitory concentration) for activity, below which no effect is seen. Without this property, antimicrobial peptides would not be effective self-defense weapons, because they would have harmed all cells at any concentration. The question is what gives rise to this unique property? This study provides a free energy description for the origin of a threshold concentration. The same free energy applied differently also explains the binding of drugs that shows no threshold concentrations. The idea is compared with theories of micellar solutions that require a large oligomer size (n 15) to achieve a threshold concentration. The elasticity of lipid bilayers makes the phenomena in membranes different. The majority of antimicrobial peptides have a large negative binding energy to the bilayer interface, but the binding causes an expansion in the membrane area, or equivalently a thinning in the membrane thickness. This elastic energy of membrane thinning elevates the energy level of interfacial binding with the peptide concentration, hence gives rise to a threshold concentration for forming pores containing as few as four peptides.

Topics: Alamethicin; Algorithms; Animals; Antimicrobial Cationic Peptides; Bees; Curcumin; Elasticity; Lipid Bilayers; Melitten; Models, Molecular; Phosphatidylcholines; Thermodynamics

Drug-membrane interactions are well known but poorly understood. Here we describe dual measurements of membrane thickness change and membrane area change due to the binding of the amphipathic drug curcumin. The combined results allowed us to analyze the binding states of a drug to lipid bilayers, one on the water-membrane interface and another in the hydrocarbon region of the bilayer. The transition between the two states is strongly affected by the elastic energy of membrane thinning (or, equivalently, area stretching) caused by interfacial binding. The data are well described by a two-state model including this elastic energy. The binding of curcumin follows a common pattern of amphipathic peptides binding to membranes, suggesting that the binding states of curcumin are typical for amphipathic drugs.

Topics: Binding Sites; Carbocyanines; Curcumin; Dimethyl Sulfoxide; Lipid Bilayers; Membrane Fluidity; Models, Chemical; Phosphatidylcholines; Phosphatidylethanolamines; Rhodamines; Unilamellar Liposomes

Interaction of curcumin with lipid bilayers is not well understood. A recent experiment showed that curcumin significantly affected the single-channel lifetime of gramicidin in a 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) bilayer without affecting its single-channel conductance. We performed two experiments to understand this result. By isothermal titration calorimetry, we measured the partition coefficient of curcumin binding to DOPC bilayers. By x-ray lamellar diffraction, we measured the thickness change of DOPC bilayers as a function of the curcumin/lipid ratio. A nonlinear membrane-thinning effect by curcumin was discovered. The gramicidin data were qualitatively interpreted by the combination of isothermal titration calorimetry and x-ray results. We show that not only does curcumin thin the lipid bilayer, it might also weaken its elasticity moduli. The result implies that curcumin may affect the function of membrane proteins by modifying the properties of the host membrane.

Topics: Computer Simulation; Curcumin; Lipid Bilayers; Membrane Fluidity; Models, Chemical; Models, Molecular; Molecular Conformation; Phosphatidylcholines