Skin barrier simulation

SNIC 2019/3-215


SNIC Medium Compute

Principal Investigator:

Lars Norlen


Karolinska Institutet

Start Date:


End Date:


Primary Classification:

10603: Biophysics



The project aims at simulating drug diffusion through a model of the human skin barrier, as well as its formation. During the last proposal period all-atom simulations have been utilized in the development of a method for calculating the partitioning of all components in topically applied drug formulations, in order to correctly assess their effect on the permeability across the skin barrier. Two separate manuscripts, one for the atomic model and one for the permeability calculations without drug formulations have been published. Coarse-grained simulations have been utilized in order to model the formation steps in-between the early stage structures (previously published in two separate publications) and the final barrier structure. A coarse-grained model of the skin barrier structue have been developed with a new version of the Martini coarse-grained force field, and preliminary permeability calculations using this model have been performed. Accurate all-atom simulations of the partitioning into the skin barrier structure are very time consuming so our next step is to investigate if we can utilize the coarse-grained Martini force field in order to do preliminary prediction of the partitioning, before we apply the slower all-atom simulations. Additionally, we will now perform extensive simulations of permeability and partitioning of transdermal formulation components in order to assess the effect of penetration enhancers.