Vesicles made of glycophospholipids with homogeneous (two fluorocarbon or two hydrocarbon) or heterogeneous (one fluorocarbon and one hydrocarbon) hydrophobic double chains

Abstract

The vesicle-forming ability of the new anionic double chain glycophospholipids 1-4, with either two hydrocarbon or two perfluorocarbon chains, or a mixed double chain (one fluorinated, one hydrogenated), was investigated. When dispersed in water, 1a-c,e, 2b,c and 4b,c readily gave heat-sterilizable vesicles, 30-70 nm in diameter. The galactose and mannose-based fluorinated vesicles were also highly stable on aging. The 6-substituted glucose derivatives 3 formed tubules that reversibly interconverted into vesicles, depending on temperature. The leakage rate in buffer of carboxyfluorescein or calcein from vesicles made from 1a-c,e 2b,c and 4b,c depended on the sugar (t1/2 galactose > mannose > glucose). It decreased significantly with increasing fluorination and length of the hydrophobic tails. The mixed perfluorocarbon/hydrocarbon-tailed amphiphiles were found to be miscible with both the two fluorocarbon chains and the two hydrocarbon chains derivatives. Such admixing tended, however, to increase the small unilamellar vesicles' permeability. In buffered serum, all the vesicles investigated were highly permeable, but incorporation of cholesterol or DSPC in vesicles made of 1e significantly reduced their permeability in serum. The new vesicle and membrane components have i.v. maximum tolerated doses as high as 500 mg/kg body weight in mice; hemolytic activity sharply decreases with increasing degree of fluorination.

Small-Angle Scattering and Electron Microscopy Investigation of Nanotubules Made from a Perfluoroalkylated Glucophospholipid

“…Perfluoroalkylated amphiphiles (F-amphiphiles) have unique properties including very high surface activities, very low critical micelle concentrations (cmc) (4,5), and enhanced tendency to self-assemble into supramolecular aggregates (3). Among the F-amphiphiles that have recently been synthesized, those with a polar head group of the phosphoglucoside-type are susceptible of being recognized by specific receptors and could therefore be utilized for targeting drugs and other agents to specific tissues (6,7). Both the alcoholic hydroxyl groups and the acid phosphate group present in phosphoglucosides can be used to bind drugs and facilitate their incorporation into drug delivery systems.…”

Effect of Fluorine Substitution on the Interaction of Lipophilic Ions with the Plasma Membrane of Mammalian Cells

“…Fluorinated liposomal drug carriers and fluorocarbon emulsions exhibit excellent biocompatibility, low toxicity, and extended blood circulation times (Gadras et al, 1999). Compared with conventional phospholipid vesicles, fluorinated liposomes show strongly reduced membrane permeability, sharply decreased hemolytic activity, increased resistance to detergents, and a modified ability to bind negatively charged proteins and lipophilic ions (e.g., tetraphenylborate, TPB Ϫ ) (Guillod et al, 1996;McIntosh et al, 1996).…”

Polyphilic Interactions as Structural Driving Force Investigated by Molecular Dynamics Simulation (Project 7)

“…Another interesting effect of the incorporation of fluorinated chains is their impact on liposome gel regarding liquid-crystalline phase-transition temperatures Tm. Although the incorporation of fluorinated chains in liposome bilayers can increase the characteristic gel to the liquid-crystalline phase-transition temperature (Tm), this effect is highly dependent on other structural features, which include the length, relative proportions and symmetry of the fluorinated segments in the bilayer [55,56].…”