Multiscale Modeling of Skin Electroporation

Area of Science:

• Biophysics
• Pharmacology
• Materials Science

Background:

• Human skin acts as a barrier to topical drug delivery, with slow permeation into deeper layers.
• Higher-molecular-weight, charged, or hydrophilic drugs require breaching the skin barrier for effective delivery.
• Electroporation enhances drug permeation and reduces lag time, but its mechanism requires further understanding.

Purpose of the Study:

• To develop a multiscale model of skin electroporation to elucidate the underlying mechanisms of enhanced drug permeation.
• To connect molecular-level phenomena with macroscopic models for a comprehensive understanding of skin electroporation.
• To provide a validated framework for the in silico design and optimization of skin electroporation experiments.

Main Methods:

• Molecular dynamics simulations of the human stratum corneum lipid matrix under electric fields to study pore formation and drug diffusivity.
• Development of a finite element method (FEM) model of the skin stratum corneum for macroscopic simulation.
• Comparison of simulated fentanyl release with experimental data to validate the multiscale model.

Main Results:

• Molecular dynamics simulations showed increased drug diffusivity due to electroporation-induced pores, higher than passive diffusion.
• The FEM model, when validated against experimental results, demonstrated comparable pore formation and a significant increase in drug flux under electric fields.
• The multiscale framework successfully predicted experimental observations of pore formation and enhanced drug permeation.

Conclusions:

• The developed multiscale model provides valuable molecular and macroscopic insights into skin electroporation.
• The validated framework can be used as a design tool for optimizing electric pulse parameters (voltage, duration, number) for enhanced transdermal drug delivery.
• This approach facilitates the design of more effective skin electroporation experiments and applications.