Mechanistic Insights Into Skin Permeation: A Physiologically Based Toxicokinetic (PBTK) Approach

Skin permeation is a critical factor in various fields, including drug delivery, cosmetic safety evaluation, and environmental pollutant exposure. Driven by ecological and production-related considerations, it is imperative to examine the effects of certain xenobiotics on organisms when exposed to specific environments. However, traditional methods for studying skin permeation often rely on empirical models or animal testing, which have limitations in terms of accuracy and ethical concerns. Besides, the analytical results are contingent upon the chosen model, and the corresponding parameters may exhibit significant variability, making it challenging to determine the most appropriate model. In response to these challenges, the physiologically based toxicokinetics (PBTK) model has been proposed, featuring a structural framework that systematically integrates all parameters governing absorption, distribution, metabolism, and excretion (ADME). Given its significant importance in the research domain, this paper provides a comprehensive review of the application of PBTK models in skin permeation studies. It is intended to serve as a valuable resource for subsequent research and to contribute to the protection of public health and safety.