In Silico Prediction of Stratum Corneum Partition Coefficients via COSMOmic and Molecular Dynamics Simulations

Stratum corneum (SC) is the main barrier of human skin
where the
inter-corneocytes lipids provide the main pathway for transdermal
permeation of functional actives of skin care and health. Molecular
dynamics (MD) has been increasingly used to simulate the SC lipid
bilayer structure so that the barrier property and its affecting factors
can be elucidated. Among reported MD simulation studies, solute partition
in the SC lipids, an important parameter affecting SC permeability,
has received limited attention. In this work, we combine MD simulation
with COSMOmic to predict the partition coefficients of dermatologically
relevant solutes in SC lipid bilayer. Firstly, we run MD simulations
to obtain equilibrated SC lipid bilayers with different lipid types,
compositions, and structures. Then, the simulated SC lipid bilayer
structures are fed to COSMOmic to calculate the partition coefficients
of the solutes. The results show that lipid types and bilayer geometries
play a minor role in the predicted partition coefficients. For the
more lipophilic solutes, the predicted results of solute partition
in SC lipid bilayers agree well with reported experimental values
of solute partition in extracted SC lipids. For the more hydrophilic
molecules, there is a systematical underprediction. Nevertheless,
the MD/COSMOmic approach correctly reproduces the phenomenological
correlation between the SC lipid/water partition coefficients and
the octanol/water partition coefficients. Overall, the results show
that the MD/COSMOmic approach is a fast and valid method for predicting
solute partitioning into SC lipids and hence supporting the assessment
of percutaneous absorption of skin care ingredients, dermatological
drugs as well as environmental pollutants.