Modelling skin permeability in risk assessment--the future.

Area of Science:

• Dermal toxicology and pharmacology
• Computational chemistry and biophysics
• Drug delivery systems

Background:

• Skin permeability modeling is vital for transdermal drug delivery, cosmetics, and toxicological risk assessment.
• Current methods include quantitative structure-activity relationships (QSARs) for permeability coefficients and mathematical modeling for substance permeation.
• Significant advancements are needed to improve predictive accuracy.

Purpose of the Study:

• To assess recent progress in skin permeability modeling.
• To identify future research directions and requirements for enhanced predictive capabilities.
• To highlight the need for integrated approaches combining exposure, penetration, and systemic factors.

Main Methods:

• Review and analysis of existing quantitative structure-activity relationships (QSARs) for predicting skin permeability.
• Evaluation of mathematical modeling techniques based on partition and transport equations.
• Discussion of data requirements for improving predictive models.

Main Results:

• Quantitative structure-activity relationships (QSARs) have yielded only modest improvements despite considerable effort.
• Further advancements necessitate new data collected under controlled conditions and novel QSAR equations.
• Existing mathematical models require integration with exposure and systemic factors for reliable risk assessment.

Conclusions:

• Significant improvements in predicting percutaneous permeability require new experimental data and advanced QSAR models.
• Reliable risk assessments for dermal exposure necessitate integrated mathematical models encompassing exposure, penetration, and systemic processes.
• Future research should focus on developing comprehensive models that bridge in vitro predictions with in vivo outcomes.