title: 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.
authors.affiliation: Unité de Chimie Moléculaire, Université de Nice-Sophia Antipolis, CNRS URA 426, Nice, France.
authors.forename: F
authors.initials: F
authors.lastname: Guillod
authors.forename: J
authors.initials: J
authors.lastname: Greiner
authors.forename: J G
authors.initials: JG
authors.lastname: Riess
mesh_terms: D000818:Animals; D001769:Blood; D002021:Buffers; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003460:Crystallization; D004355:Drug Stability; D005461:Fluorine / Q000737:chemistry*; D005690:Galactose / Q000032:analysis; D005782:Gels; D005947:Glucose / Q000032:analysis; D006017:Glycolipids / Q000737:chemistry* / Q000633:toxicity; D006461:Hemolysis; D006358:Hot Temperature; D006801:Humans; D006865:Hydrogenation; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D008358:Mannose / Q000032:analysis; D051379:Mice; D010743:Phospholipids / Q000737:chemistry* / Q000633:toxicity; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics
chemical_list: D002021:Buffers; D005782:Gels; D006017:Glycolipids; D008081:Liposomes; D010743:Phospholipids; D005461:Fluorine; D005947:Glucose; D008358:Mannose; D005690:Galactose