E/M dips. Evidence for lipids regularly distributed into hexagonal super-lattices in pyrene-PC/DMPC binary mixtures at specific concentrations.

We have examined the effect of 1-palmitoyl-2-(10-pyrenyl)decanoyl-sn-glycerol-3-phosphatidylcholine (Pyr-PC) concentration on the ratio of excimer fluorescence to monomer fluorescence (E/M) in L-alpha-dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles at 30 degrees C, with special attention focussed on the smoothness of the curve. We observed a series of dips, in addition to kinks, in the plot of E/M versus the mole fraction of Pyr-PC (XPyrPC). The observation of dips is a new finding, perhaps unique for Pyr-PC in DMPC since only kinks were observed for Pyr-PC in L-alpha-dipalmitoylphosphatidylcholine (DPPC) and in egg yolk phosphatidylcholine (egg-PC) (Somerharju et al., 1985. Biochemistry. 24: 2773-2781). The dips/kinks observed here are distributed according to a well defined pattern reflecting a lateral order in the membrane, and distributed symmetrically with respect to 50 mol% Pyr-PC. Some of the dips appear at specific concentrations (YPyrPC) according to the hexagonal super-lattice model proposed by Virtanen et al. (1988. J. Mol. Electr. 4: 233-236). However, the observations of dips at XPyrPC > 66.7 mol% and the kink at 33.3 mol% cannot be interpreted by the model of Virtanen et al. (1988). These surprising results can be understood by virtue of an extended hexagonal super-lattice model, in which we have proposed that if the pyrene-containing acyl chains are regularly distributed as a hexagonal super-lattice in the DMPC matrix at a specific concentration YPyrPC, then the acyl chains of DMPC can form a regularly distributed hexagonal super-lattice in the membrane at a critical concentration (1-YPyrPC).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of chirality on PVP/drug interaction within binary physical mixtures of ibuprofen, ketoprofen, and naproxen: a DSC study

We report on the thermal behavior of freshly prepared binary drug/polymer physical mixtures that contained ibuprofen, ketoprofen, or naproxen as a drug, and polyvinylpyrrolidone (PVP), hydroxyethylcellulose (HEC), or methylcellulose (MC) as excipient. At 6-10 degrees C/min heating rates the DSC detected a sharp, single endotherm that corresponds to the melting of drug. On heating physical mixtures of PVP and racemic ibuprofen or ketoprofen at lower heating rates, another endotherm was registered in front of the original one. To observe the additional endotherm, specific minimal values of the heating rate and of PVP weight fraction were needed; for ibuprofen and ketoprofen they were 1.5 and 2.0 degrees C/min, and 5 and 15% (w/w), respectively. At greater PVP weight fractions the top temperatures, T(mp), of both peaks were reduced almost linearly indicating strong solid-state interfacial reaction between the drug particles and PVP matrix. The additional endotherm was abolished at greater heating rates (2 degrees C/min for ibuprofen, 3 degrees C/min for ketoprofen), by replacing the racemate with respective S+-enantiomer and by replacing PVP with HEC and MC. Hence, the possible inclusion of enantioselective component within the PVP/drug interaction, responsible for the amorphization of physical mixture over storage, is assumed.     

Fast laser-induced solute release from liposomes sensitized with photochromic lipid: effects of temperature, lipid host, and sensitizer concentration.

Liposomes of gel-phase phospholipid have been prepared containing a photochromic lipid sensitizer. A fast UV laser pulse isomerizes the sensitizer destabilizing the lipid bilayer structure and causing release of trapped solute. The kinetics of solute release have been investigated as a function of host lipid chain length, sensitizer concentration, and temperature, and the limits of liposome stability have been established. At low concentrations of sensitizer, pulsed laser irradiation induces some solute release when continuous UV illumination is ineffective. Although rates of solute release usually increase with temperature, at low sensitizer concentration in a rigid host, leakage at first increases but then decreases rapidly above a threshold temperature. The results presented are relevant to the design of photostimulated drug delivery systems and to potential applications of photosensitive liposomes as caging agents for biological effectors.     

Changes of the physical properties of the liquid-ordered phase with temperature in binary mixtures of DPPC with cholesterol: A 2H-NMR, FT-IR, DSC, and neutron scattering study

The structure of the so-called liquid-ordered (lo) phase of binary mixtures of DPPC-d₆₂ with cholesterol was studied between 20-50 mol% cholesterol using ²H-NMR, FT-IR, DSC, and neutron specular reflection. Different model systems such as multilamellar vesicles, spherical supported vesicles, and oriented multilayers were used. We observed significant changes of the lo phase structure in the physiological relevant temperature region between 30-45°C. ²H-NMR in combination with lineshape simulations provides evidence for a drastic effect of cholesterol on the shape of multilamellar vesicles due to magnetic field orientation. Moreover, the data indicates a significant change of the extent of this partial orientation for DPPC-d₆₂ multilamellar vesicles containing 25 mol% cholesterol between 36-42°C. The semiaxes ratio of the (due to magnetic field orientation) ellipsoidal multilamellar vesicles changes over this temperature range by ≈25%. ²H-NMR and FT-IR measurements indicate changes of the average orientational order at the bilayer center in the same temperature range and a significant increase of the number of end-gauche conformers while the majority of the methylene groups remain in an all-trans conformation. Additionally, specular reflection of neutrons shows a concomitant reduction of the bilayer thickness by 4 Å. Based on a model of the arrangement of DPPC and cholesterol in the lo phase, a molecular mechanism is proposed in which increasing the temperature between 30 and 45°C has the effect of driving cholesterol from the bilayer center towards the head group region.     

Partitioning and membrane disordering effects of dopamine antagonists: influence of lipid peroxidation, temperature, and drug concentration.

The effect of four dopamine antagonists (spiperone, haloperidol, pimozide, and domperidone) on the lipid order of caudate nucleus microsomal membranes and on liposomes from membrane lipid extracts was evaluated and related to the partition coefficients (Kp) of the drugs. Lipid membrane order was determined by fluorescence polarization using 1,6-diphenyl-1,3,5-hexatriene (DPH) as a probe of the membrane core and 1-[4-(trimethylammonium)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH) as a probe of the membrane surface. Dopamine antagonists decrease the fluorescence polarization of both probes, indicating that they disorder the membrane lipids at different depths. Pimozide and domperidone, the drugs with higher Kp values, are more effective at decreasing the polarization of DPH, a probe of the membrane core, than that of TMA-DPH. In contrast, spiperone and haloperidol, which have lower values for Kp, induce more significant decreases in TMA-DPH depolarization, a probe of the membrane surface. These findings indicate that higher partition coefficients of the drugs are directly correlated with an increase of fluidity in the hydrophobic core of brain membranes. Ascorbate/Fe(2+)-induced membrane lipid peroxidation increases membrane order. Membrane lipid peroxidation decreases the partition coefficients of the dopamine antagonists tested. Increasing temperature (4-37 degrees C) decreases membrane order, but temperature effect is less evident after lipid peroxidation. The disordering effect of dopamine antagonists increases with increasing drug concentrations (1-15 microM), a maximum being observed at 10 microM. However, this effect is also less evident after membrane lipid peroxidation. We can conclude that dopamine antagonists and membrane lipid peroxidation affect membrane lipid order and that the action of these drugs is dependent on initial bilayer fluidity. Membrane lipid peroxidation increases membrane order while dopamine antagonists show a disordering effect of membrane phospholipids. This disordering effect can indirectly influence the activity of membrane proteins and it is one of the mechanisms through which membrane function can be altered by these drugs.     

Ecological investigations on the zooplankton community in Balsfjorden,Northern Norway: seasonal changes in the lipid class composition of Meganyctiphanes norvegica (M. Sars), Thysanoessa raschii (M. Sars), and T. inermis (Krøyer)

The lipid class composition of three krill species, Meganyctiphanes norvegica (M. Sars), Thysanoessa raschii (M. Sars), and T. inermis (Krøyer), was determined throughout the year in Balsfjorden, Northern Norway. Meganyctiphanes norvegica had triglycerides as its major neutral lipid, Thysanoessa raschii had mainly triglycerides with small amounts of wax esters, whereas T. inermis had mainly wax esters with lesser amounts of triglycerides. Neutral lipids were generally accumulated by the krill during spring-early summer, maintained at high levels through to mid-winter and then declined to minimal levels during early spring. Differences in rates of deposition and mobilization of neutral lipid between males and females occurred in Meganyctiphanes norvegica and Thysanoessa raschii but not in T. inermis. T. raschii accumulated lipid somewhat later in the year than T. inermis but earlier than Meganyctiphanes norvegica. A major rôle for lipid in the elaboration of gonads is indicated. The accumulation of either wax esters or triglycerides by euphausiids is considered in terms of the feeding habits and ecological niche differentiation of the species.