1-2-oleoylphosphatidylcholine and 1-stearoyl-2-linoleoylphosphatidylcholine

Photo-triggerable liposomes are considered nowadays as promising drug delivery devices due to their potential to release encapsulated drugs in a spatial and temporal manner. In this work, we have investigated the photopermeation efficiency of three photosensitizers (PSs), namely verteporfin, pheophorbide a and m-THPP when incorporated into liposomes with well-defined lipid compositions (SOPC, DOPC or SLPC). By changing the nature of phospholipids and PSs, the illumination of the studied systems was shown to significantly alter their lipid bilayer properties via the formation of lipid peroxides. The system efficiency depends on the PS/phospholipid association, and the ability of the PS to peroxidize acyl chains. Our results demonstrated the possible use of these three clinically approved (or under investigation) PSs as potential candidates for photo-triggerable liposome conception.

Topics: Chlorophyll; Drug Liberation; Fluoresceins; Fluorescent Dyes; Hydrophobic and Hydrophilic Interactions; Light; Lipid Bilayers; Lipid Peroxidation; Liposomes; Mesoporphyrins; Molecular Dynamics Simulation; Permeability; Phosphatidylcholines; Photosensitizing Agents; Porphyrins; Transition Temperature; Verteporfin

Saturated phospholipids (PCs), particularly dipalmitoylphosphatidylcholine (DPPC), predominate in surfactant lining the alveoli, although little is known about the relationship between saturated and unsaturated PCs on the outer surface of the lung, the pleura. Seven healthy cats were anesthetized and a bronchoalveolar lavage (BAL) was performed, immediately followed by a pleural lavage (PL). Lipid was extracted from lavage fluid and then analyzed for saturated, primarily dipalmitoylphosphatidylcholine (DPPC), and unsaturated PC species using high-performance liquid chromatography (HPLC) with combined fluorescence and ultraviolet detection. Dilution of epithelial lining fluid (ELF) in lavage fluids was corrected for using the urea method. The concentration of DPPC in BAL fluid (85.3+/-15.7 microg/mL) was significantly higher (P=0.021) than unsaturated PCs ( approximately 40 microg/mL). However, unsaturated PCs ( approximately 34 microg/mL), particularly stearoyl-linoleoyl-phosphatidylcholine (SLPC; 17.4+/-6.8), were significantly higher (P=0.021) than DPPC (4.3+/-1.8 microg/mL) in PL fluid. These results show that unsaturated PCs appear functionally more important in the pleural cavity, which may have implications for surfactant replenishment following pleural disease or thoracic surgery.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Animals; Body Fluids; Bronchoalveolar Lavage Fluid; Cats; Female; Leukocytes; Male; Phosphatidylcholines; Phospholipids; Pleura; Pleural Cavity; Pulmonary Surfactants

Detergent-insoluble membrane domains, enriched in saturated lipids and cholesterol, have been implicated in numerous biological functions. To understand how cholesterol promotes domain formation, the effect of various sterols and sterol derivatives on domain formation in mixtures of the saturated lipid dipalmitoylphosphatidylcholine (DPPC) and a fluorescence quenching analogue of an unsaturated lipid was compared. Quenching measurements demonstrated that several sterols (cholesterol, dihydrocholesterol, epicholesterol, and 25-hydroxycholesterol) promote formation of DPPC-enriched domains. Other sterols and sterol derivatives had little effect on domain formation (cholestane and lanosterol) or, surprisingly, strongly inhibit it (coprostanol, androstenol, cholesterol sulfate, and 4-cholestenone). The effect of sterols on domain formation was closely correlated with their effects on DPPC insolubility. Those sterols that promoted domain formation increased DPPC insolubility, whereas those sterols that inhibit domain formation decreased DPPC insolubility. The effects of sterols on the fluorescence polarization of diphenylhexatriene incorporated into DPPC-containing vesicles were also correlated with sterol structure. These experiments indicate that the effect of sterol on the ability of saturated lipids to form a tightly packed (i.e., tight in the sense that the lipids are closely packed with one another) and ordered state is the key to their effect on domain formation. Those sterols that promote tight packing of saturated lipids promote domain formation, while those sterols that inhibited tight packing of saturated lipids inhibited domain formation. The ability of some sterols to inhibit domain formation (i.e., act as "anti-cholesterols") should be a valuable tool for examining domain formation and properties in cells.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Cholestanes; Cholesterol; Diphenylhexatriene; Fluorescence Polarization; Lanosterol; Lipid Bilayers; Membrane Lipids; Octoxynol; Phosphatidylcholines; Solubility; Spectrometry, Fluorescence; Sterols; Structure-Activity Relationship; Temperature

The partitioning of native cytochrome b5 and a mutant form, where Trp-108 and Trp-112 were both replaced by Leu, into small unilamellar lipid vesicles was examined. The vesicles were made from phosphatidylcholines containing mono- and di-unsaturated acyl chains. As these amphipathic proteins self-associate in aqueous solution, the binding was not monitored by a simple lipid titration experiment but by an exchange assay using fluorescence quenching by brominated lipids. Each protein had a greater affinity for lipids containing mono-unsaturated chains than for vesicles containing di-unsaturated chains, and the affinities of both proteins increased in buffers of higher ionic strength. The native protein had a higher affinity than the mutant protein for all vesicles; the ratio of the affinities was relatively constant at approximately 30. This corresponds to a difference in the free energy of partitioning of 2 kcal mol(-)(1). The fluorescence quantum yields of both proteins were much lower in lipids with di-unsaturated chains whereas a similar lowering was not seen with a simple Trp compound. These data suggest that the decreased membrane hydrophobicity seen by the proteins in di-unsaturated membranes is not an inherent property of the bilayer but is induced by the insertion of the protein. Further, the similar behavior of the two proteins suggests this modulation is not sensitive to the amino acid side chains of the inserted domain.

Topics: Bromine; Chromatography, Gel; Cytochromes b5; Escherichia coli; Fluorescent Dyes; Lipid Bilayers; Membrane Proteins; Mutagenesis, Site-Directed; Osmolar Concentration; Phosphatidylcholines; Protein Binding; Spectrometry, Fluorescence; Tryptophan