(674d) Effect of Incorporation of Lysolipid on Dipalmitoylphosphatidylcholine Bilayer Membrane: Study on the Permeability Enhancement of Liposomes at the Phase Transition Using Molecular Dynamics Simulations

Drug delivery and its release depend greatly on the ability to control the permeability of the vesicle encapsulating the drug. Liposomes, which are spherical nanoparticles composed of one or more phospholipid bilayers, have emerged as a promising delivery system for potent chemotherapeutics. It is well known that the permeability of drug through lipid bilayers exhibits a maximum as the lipid bilayer undergoes the transition from gel to liquid-crystalline phase, which has been studied intensively in order to control the permeability. One of the ways for the controlled drug release is an addition of the lysolipid, which affects the transition properties such as temperature. 

In this study, we run fully atomistic molecular dynamics (MD) simulation with flat liposome model comprised of both DiPalmitoyl Phosphatidyl Choline (DPPC) and 0-30% lysolipids of MonoPalmitoyl Phoshatidyl Choline (MPPC). The phase transition temperature is obtained by monitoring the area per lipid and the lateral diffusion coefficient as the temperature is changed. At this phase transition temperature, we examine the structural characteristic of the mixed system by observing the density profile and interfacial tension profile. Furthermore, to clarify the mechanism of enhanced drug release of lysolipid containing liposome, we investigate the most probable distribution of MPPC in the mixed membrane, which could be in the form of either dispersed or assembled configuration.