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Lateral Diffusion Rates of Lipid, Water, and a Hydrophobic Drug in a Multilamellar Liposome

Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland

Correspondence: Address reprint requests to Klaus Gawrisch, Laboratory of Membrane Biochemistry and Biophysics, NIAAA, National Institutes of Health, 12420 Parklawn Dr., Rm. 150, Rockville, MD 20852. Tel.: 301-594-3750; Fax: 301-594-0035; E-mail: gawrisch{at}helix.nih.gov.

The lateral diffusion constants of 1-palmitoyl-2-oleoyl-sn-glycero-3 phosphocholine (POPC), water, and ibuprofen were measured in multilamellar liposomes using pulsed field gradient magic-angle spinning (PFG-MAS) ¹H NMR. The analysis of diffusion data obtained in powder samples and a method for liposome curvature correction are presented. At 322 K POPC has a diffusion constant of (8.6 ± 0.2) x 10^-12 m²/s when dehydrated (8.2 waters/lipid) and (1.9 ± 0.1) x 10^-11 m²/s in excess water. The diffusion constant of water in dehydrated POPC was found to be (4.7 ± 0.1) x 10^-10 m²/s. The radius of curvature is 21 ± 2 µm for the dehydrated sample and 4.5 ± 0.5 µm for POPC sample containing excess water. The activation energies of diffusion are 40.6 ± 0.4 kJ/mole for dehydrated POPC, 30.7 ± 0.9 kJ/mole for POPC with excess water, and 28.6 ± 1.5 kJ/mole for water in dehydrated POPC. The diffusion constants and activation energies for a sample of POPC/ibuprofen/water (1:0.56:15) were also measured. The ibuprofen, which locates in the lipid-water interface, diffuses faster than POPC but has a slightly higher activation energy of lateral diffusion. Within certain restrictions, PFG-MAS NMR provides a useful method for characterizing membrane organization and mobility.

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