Abstract
In order to develop drug delivery systems (DDS) using liposomes, it is important to understand the effects of mechanical stresses on the water permeability of liposomes. We perform a series of molecular dynamics simulations of stretched palmitoyl-oleoyl phosphatidylcoline (POPC) lipid bilayers, which is the fundamental shell component of the liposomes. The stretched bilayers are simulated by constant temperature and bilayer normal pressure MD simulations with various constant areas. Under stretching, the bilayer thickness becomes thin. In the core of the bilayer, the lipid density increases, resulted in the smaller diffusion coefficient and the larger potential of mean force of water in the core region. This leads to the increase in the local resistance for water permeation. However, the apparent water permeability, which is the inverse of the integrated value of the resistance profile across the bilayer, shows the increase trend as the thickness decreases, although it depends on the applied stretch. This indicates that the water permeability and the permeation mechanism might be affected by mechanical stresses. As the DDS liposomes experience various mechanical stresses during blood circulation, it may be important to evaluate the leakage of drugs from the liposome considering the history of the stresses and the apparent permeability change.
