A Sucrose Solution Application to the Study of Model Biological Membranes

The small-angle X-ray and neutron scattering, time resolved X-ray small-angle and wide-angle diffraction coupled with differential scanning calorimetry have been applied to the investigation of unilamellar and multilamellar dimyristoylphosphatidylcholine (DMPC) vesicles in sucrose buffers with sucrose concentrations from 0 to 60%. Sucrose buffer decreased vesicle size and polydispersity and increased an X-ray contrast between phospholipid membrane and bulk solvent sufficiently. No influence of sucrose on the membrane thickness or mutual packing of hydrocarbon chains has been detected. The region of sucrose concentrations 30%-40% created the best experimental conditions for X-ray small-angle experiments with phospholipid vesicles.Comment: PDF: 10 pages, 6 figures. MS Word sours

Intérêts et limites du Glivec® dans le traitement de la leucémie myéloide chronique

AIX-MARSEILLE2-BU Pharmacie (130552105) / SudocSudocFranceF

Phospholipid bilayer perturbing-properties underlying lysis induced by pH-sensitive cationic lysine-based surfactants in biomembranes

Many strategies for treating diseases require the delivery of drugs into the cell cytoplasm following internalization within endosomal vesicles. Thus, compounds triggered by low pH to disrupt membranes and release endosomal contents into the cytosol are of particular interest. Here, we report novel cationic lysine-based surfactants (hydrochloride salts of Nε- and Nα-acyl lysine methyl ester) that differ in the position of the positive charge and the length of the alkyl chain. Amino acid-based surfactants could be promising novel biomaterials in drug delivery systems, given their biocompatible properties and low cytotoxic potential. We examined their ability to disrupt the cell membrane in a range of pH values, concentrations and incubation times, using a standard hemolysis assay as a model of endosomal membranes. Furthermore, we addressed the mechanism of surfactant-mediated membrane destabilization, including the effects of each surfactant on erythrocyte morphology as a function of pH. We found that only surfactants with the positive charge on the α-amino group of lysine showed pH-sensitive hemolytic activity and improved kinetics within the endosomal pH range, indicating that the positive charge position is critical for pH-responsive behavior. Moreover, our results showed that an increase in the alkyl chain length from 14 to 16 carbon atoms was associated with a lower ability to disrupt cell membranes. Knowledge on modulating surfactant-lipid bilayer interactions may help us to develop more efficient biocompatible amino acid-based drug delivery devices