A Comparative Analysis of Biological and Synthetic Skin Models for Drug Transport Studies

Ethical restrictions as well as practical or economic issues related to use of animal and human skin has been the main reason the growth in the number of investigations with alternative models. Reconstructed skin models, for example, have been useful to evaluate the in vitro toxicity of compounds; however, these models usually overestimate the amount of drug permeated due to impaired barrier properties. In this review, the performance of synthetic and biological skin models in transport studies was compared by considering two compounds with different physicochemical properties. The advantages and limitations of each skin model are discussed in detail. Although synthetic and reconstructed skin models have shown to be useful in the formulation optimization step, they present many limitations: (1) impaired barrier properties; (2) lack of follicular transport; (3) no metabolism in synthetic membranes; (4) differences in terms of lipid organization; (5) more affected by formulation constituents. Therefore, animal and human tissues should still be prioritized in drug transport studies until new advances in alternative models are achieved. Investigations of the impact of cell-culture conditions on skin formation, in turn, bring perspectives related to the development of unhealthy/injured skin models (an aspect that still deserves attention). Graphical Abstract