Abstract
Skin acts as a dynamic interface with the environment. Pathological alterations in the skin barrier are associated with skin diseases. These conditions are characterized by specific impairments in epidermal barrier functions. Despite its protective nature, the skin can be a relevant route of drug administration, both for topical and transdermal therapy, allowing for improved drug delivery and reducing the incidence of adverse reactions. This manuscript reviews transcutaneous drug delivery as a strategy for treating localized and systemic conditions, highlighting the importance of skin models in the evaluation of drug efficacy and barrier function. It explores advances in in vitro, ex vivo, in vivo, and in silico models for studying cellular uptake, wound healing, oxidative stress, anti-inflammatory, and immune modulation activities. Disease-specific skin models are also discussed.