Critical evaluation and methodological positioning of the transdermal microdialysis technique. A review

Transdermal or as also referred to cutaneous or skin microdialysis is a sampling and monitoring technique for testing drug concentrations in the extracellular fluid of the skin, has been developed during the last decades. Its early applications aimed to determine the transdermal drug delivery by pharmacokinetic and/or toxicokinetic characterization of drug penetration through the skin. Being a minimally invasive technique its employment in human volunteers run in parallel with the preclinical animal experiments. With the discovery of topical drug absorption enhancers (both active and passive) it became more and more important to study the dermal absorption of the unbound, pharmacologically active form of certain molecules in vivo in the living tissue. This review gives an overview about iontophoretic drug delivery studies and also on the assessment of dermal drug formulations followed and evaluated by transdermal microdialysis. The new foci of the application of skin microdialysis techniques are the drug transporter interaction studies on the cutaneous barrier and the disease-related biomarker studies in dermatological research. At the final part of this review complementary technologies are presented and compared with transdermal microdialysis. In summary, transdermal microdialysis technique is a traditional in vivo method for investigating the alterations of the biochemical milieu in the skin. It is an important element of the toolbox of preclinical and clinical dermal pharmacokinetic/pharmacodynamic assays. The advancement in dermatopharmacology and pharmaceutical formulation technology, disease biomarker studies and also the development of drug-drug, drug-transporter interaction research open new horizons both for the experimental and clinical applications of this assay. (C) 2016 Elsevier B.V. All rights reserved.