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

AbstractThe 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 322K POPC has a diffusion constant of (8.6±0.2)×10−12 m2/s when dehydrated (8.2 waters/lipid) and (1.9±0.1)×10−11 m2/s in excess water. The diffusion constant of water in dehydrated POPC was found to be (4.7±0.1)×10−10 m2/s. The radius of curvature is 21±2μm for the dehydrated sample and 4.5±0.5μm 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