(227b) Nanoparticle Permeation Induced Water Penetration and Ion Transport Through a Lipid Membrane

Nanoparticles are generally considered excellent candidates for targeted drug delivery. However, ion leakage and cytotoxicity induced by nanoparticle permeation is a potential problem in such drug delivery schemes because of the toxic effect of many ions. In this research, we have carried out a series of coarse-grained molecular dynamics simulations to investigate the water penetration, ion transport and lipid molecule flip-flop in a protein-free phosphor-lipid bilayer membrane during nanoparticle permeation. The effect of ion concentration, pressure differential across the membrane, nanoparticle size and permeation velocity have been examined in this work. Some conclusions from our studies include: 1) The number of water molecules in the interior of the membrane during the nanoparticle permeation increases with the nanoparticle size and the pressure differential across the membrane, but is unaffected by the nanoparticle permeation velocity or the ion concentration; 2) Ion transport is sensitive to the size of nanoparticle as well as the ion concentration difference between two sides of the membrane; We also observe no selectivity between anions and cations; 3) The lipid molecule flip-flop is directly related to the size of nanoparticle and ion concentration differential, while it is an inversely related to the pressure differential and the nanoparticle permeation velocity. The findings described in our work will lead to a better understanding of passive water and ion transport during the permeation of nanoparticle and help develop more efficient nanocarrier drug delivery systems while avoiding cell cytotoxicity for intracellular delivery of therapeutics.