Tuning the transdermal transport by application of external continuous electric field: a coarse-grained molecular dynamics study

Abstract

The control of skin permeability to specific substances (e.g., medications, vitamins, and nutrients) through stratum corneum is a challenge. Iontophoresis is an option in spite of the lack of a detailed understanding of the underlying molecular mechanism. In the present work, the simulations concerning application of an external continuous electric field to stratum corneum, in a range of low intensity (0–24 mV nm⁻¹), were carried out using the coarse-grained molecular dynamics approach. Using a set of random seed replicas of the starting configuration, we observed that in the range of electric field intensity of 22–23 mV nm⁻¹, water-rich lipid vesicles were formed in 20% of cases. Pores appeared in the remaining 80%. We argue that lipids undergo fast re-orientations under electric field inducing mechanical instability, which originates the pores. We presented a simple electrostatic model to interpret the results where the mismatch between electrical permittivities of the membrane and external media and the gradient of the local electric field in the membrane surface, govern the time scales and electric fields for vesicle formation. Our results indicate that just 10% difference between electrical permittivities of the membrane and external media decreases 1/6 the minimal time required for vesicle formation. The minimal electric field required decreases 10 times. The control and tunning of formation of biologically compatible vesicles, capable of transporting substances under low-intensity electric fields, has a promising application in fields such as drug therapy and dermo-cosmetics allowing the use of hydrophilic substances in dermal applications.