Different oxidized phospholipid molecules unequally affect bilayer packing.
(9/90)
The aim of this study was to gain more detailed knowledge about the effect of the presence of defined oxidized phospholipid molecules in phospholipid bilayers. After chromatographic and mass spectrometry analysis, the previously used product of the Fenton reaction with unsaturated lecithins proved to consist of a plethora of oxidatively modified lecithins, useless either for the detailed study of the effects brought about in the bilayer or as the source of defined oxidized phospholipid molecules. The latter, particularly 2-(omega-carboxyacyl)- and 2-(n-hydroperoxyacyl)-lecithins, can be more conveniently prepared by chemical or enzymatic synthesis rather than by chemical or physical oxidation. The effect of those molecules and of commercially available 12-hydroxy-stearic and dodecanedioic acid was studied in planar supported phospholipid bilayers (SPBs) by use of EPR spectrometry. The SPBs also contained 2-(5-doxylstearoyl)-lecithin as the spin probe, and the EPR spectral anisotropy loss, indicative of bilayer disordering, was measured as a function of the molar percentage of oxidized lipid. Most oxidized lipid molecules examined in this study were able to induce bilayer disordering, while hydroperoxyl group-bearing acyl chains appeared to be much less effective. It is concluded that the effects of different oxidized phospholipids on phospholipid bilayer structure cannot be generalized, as happens with batch-oxidized phospholipids, and that the use of defined oxidized phospholipid molecular species for membrane oxidative stress guarantees a more reliable and detailed response. (+info)
Paclitaxel solubility in aqueous dispersions and mixed micellar solutions of lecithin.
(10/90)
The aim of this study was to find a biocompatible, lecithin-based carrier for paclitaxel (PTX) suitable for intravenous infusion and ensuring a soluble PTX concentration of 100 mg/100 ml or higher for at least 24 h. Aqueous dispersions of egg or soya lecithin (water-lecithin dispersions, WLD), mixed micellar (MM) solutions of egg lecithin and sodium deoxycholate, and formulations containing lecithin plus the co-surfactants and co-solvents poloxamer, polysorbate, Span, benzalkonium chloride, and macrogol were investigated. Amorphous PTX was prepared by lyophilization. PTX co-lyophilized with surfactants was also studied. Unlike crystalline PTX, the drug in an amorphous form is easily soluble in 1-5% (w/w) WLD or in MM. The highest solubility (up to 570 mg/100 ml) was achieved in 5% WLD. Dissolved PTX precipitated from all tested formulations over 24 h. Despite this, concentrations of dissolved PTX of 100 mg/100 ml or higher were observed after 24 h in 5% egg WLD, 1-5% soya WLD, and in 5% MM (lecithin : deoxycholate ratio 1 : 1 w/w). When four different batches of 5% egg WLD were prepared, containing PTX in clinically relevant concentration of 100 mg/100 ml, no precipitation of PTX was observed within 24 h and this formulation is the most promising candidate for further in vivo studies. Neither additional surfactants nor co-lyophilization increased PTX solubility in the lecithin-based carriers. The use of parenteral emulsions as solvents for the co-lyophilized PTX also failed to increase the solubility of the drug up to the target concentration. (+info)
Using the lymph fistula rat model to study the potentiation of GIP secretion by the ingestion of fat and glucose.
(11/90)
Interleukin-4 induces lipogenesis in porcine endothelial cells, which in turn is critical for induction of protection against complement-mediated injury.
(12/90)
The method for preparation of vesicles, by evaporation of hydrophobic solvent from double emulsion (w/o/w) formed in the properly designed device is described. These method leads to multiple increase of encapsulation efficiency of aqueous solutions of drug in liposomes in comparison with other method. The w/o/w was passed through the glass sinter with the use of negative pressure to disrupt w/o/w drops into smaller ones. At low pressure and at heigher temperature, the hydrophobic solvent from oil phase evaporated off and the lipids that were diluted in oil phase had created bilayer. When the relatively small quantity of lipids was used, the final encapsulation efficiency (ee) was about 50% and the uppermost encapsulation volume (ev) was 160 mL/g of lipids. Similar ee was noted for a 4-amino-10-methylfolic acid (MTX), Patent Blue V (PB) and bovine serum albumin (BSA). Liposomes loaded with drug at high concentration may be easily separated from suspension with the use of simple centrifugation. (+info)
Intermediate phosphorylation reactions in the mechanism of ATP utilization by the copper ATPase (CopA) of Thermotoga maritima.
(15/90)