Multiscale modeling framework of transdermal drug delivery.

Area of Science:

• Pharmacology
• Materials Science
• Computational Biology

Background:

• The stratum corneum (SC) acts as the primary barrier to transdermal drug permeation.
• Reproducibility and predictability of percutaneous absorption require a deep understanding of SC barrier properties.

Purpose of the Study:

• To develop a multiscale modeling framework for transdermal diffusion of multicomponent drugs.
• To quantitatively understand the permeation barrier properties of the stratum corneum.

Main Methods:

• A multiscale approach dividing the problem into microscopic, mesoscopic, and macroscopic length scales.
• Molecular dynamics (MD) simulations to determine microscopic diffusion coefficients in SC lipid bilayers.
• Homogenization techniques to derive effective macroscopic diffusion parameters for finite element simulations.

Main Results:

• Effective diffusion parameters were obtained for the heterogeneous SC structure.
• The multiscale model successfully predicted drug flux through the skin.
• Model predictions showed strong agreement with experimental data.

Conclusions:

• The proposed multiscale framework provides a robust method for modeling transdermal diffusion.
• This approach enhances the predictability of drug permeation across the skin barrier.
• Accurate modeling is crucial for advancing transdermal drug delivery systems.