title: The effect of lipid composition on the relaxivity of Gd-DTPA entrapped in lipid vesicles of defined size.
abstract: The effects of lipid composition on the relaxivity of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) entrapped in lipid vesicles has been examined for vesicles of different sizes composed of egg phosphatidylcholine and cholesterol in various molar ratios, as well as the stability of those same vesicles in human serum at 37 degrees C. It is found that the incorporation of cholesterol decreases the apparent relaxivity of the entrapped Gd-DTPA, concomitant with an increase in vesicle stability in serum. Cholesterol has little effect on relaxivity when incorporated at ratios up to 20 mole percent, but has an increasing effect at higher mole percentages. These results correlate with the known effects of cholesterol on the osmotic water permeability coefficients of various model membrane systems and suggest that it is the water flux across the vesicle bilayer that is limiting to the T1 relaxivity of the entrapped Gd-DTPA. The incorporation of up to 20 mole percent cholesterol has little effect on the stability of the vesicles in serum, whereas vesicles containing more than 20 mole percent cholesterol show greater increases in stability. It was also found that the stability of vesicles depends upon the size of the vesicles; smaller vesicles are less stable in human serum at 37 degrees C than larger vesicles.
authors.affiliation: Department of Biochemistry, University of British Columbia, Vancouver, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Tilcock
authors.forename: P
authors.initials: P
authors.lastname: MacDougall
authors.forename: E
authors.initials: E
authors.lastname: Unger
authors.forename: D
authors.initials: D
authors.lastname: Cardenas
authors.forename: L
authors.initials: L
authors.lastname: Fajardo
mesh_terms: D001769:Blood; D002463:Cell Membrane Permeability / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002784:Cholesterol / Q000032:analysis / Q000494:pharmacology; D004355:Drug Stability; D019786:Gadolinium DTPA; D006801:Humans; D008055:Lipids / Q000032:analysis*; D008081:Liposomes / Q000032:analysis*; D009942:Organometallic Compounds; D010316:Particle Size; D004369:Pentetic Acid; D010713:Phosphatidylcholines / Q000032:analysis
chemical_list: D008055:Lipids; D008081:Liposomes; D009942:Organometallic Compounds; D010713:Phosphatidylcholines; D004369:Pentetic Acid; D002784:Cholesterol; D019786:Gadolinium DTPA