A multiple-pathway model for the diffusion of drugs in skin

Area of Science:

• Pharmacokinetics
• Mathematical Biology
• Dermatology

Background:

• Understanding drug diffusion in skin is crucial for effective topical therapies.
• Existing models may not fully capture the complexity of transdermal drug delivery.
• The skin's barrier function presents significant challenges for drug penetration.

Purpose of the Study:

• To develop a comprehensive mathematical model for drug diffusion across the skin.
• To analyze drug penetration via transcellular and intercellular routes and their interaction.
• To derive an analytical expression for steady-state drug flux to the blood.

Main Methods:

• Development of a multi-pathway diffusion model.
• Application of pharmacologically motivated asymptotic analysis.
• Steady-state flux calculation.
• Numerical simulations to validate model predictions.

Main Results:

• An analytical expression for drug flux to the blood at steady state was derived.
• The model accounts for drug movement through both cellular and between-cell pathways.
• Numerical results demonstrate the model's predictive capabilities for drug diffusion.

Conclusions:

• The developed mathematical model provides a robust framework for understanding transdermal drug diffusion.
• The analytical solution offers valuable insights into factors controlling drug delivery to systemic circulation.
• This model can aid in the design and optimization of topical drug formulations.