Although transdermal drug delivery would be very useful for the treatment of many diseases, in practice it is difficult to accomplish for the obstruction of the stratum corneum. The application of cold atmospheric plasma (CAP) as a pretreatment to the skin surface helps to enhance the delivery of topically applied drugs into the skin and the systemic circulation. CAP can change the skin properties to improve drug penetration by various different effects based on its multiple components. This review first introduces the skin barrier properties and some traditional transdermal drug delivery strategies. Next what is known about the application of CAP in transdermal drug delivery has been summarized, including the mechanisms and possible side effects. We believe that CAP could be developed as a non-invasive and efficient pretreatment to improve the transdermal permeation of drugs in clinical practice, although more research needs to be done to overcome the challenges. Graphical Abstract.
Keywords: Cold atmospheric plasma; Dielectric barrier discharge; Skin barrier; Stratum corneum; Transdermal drug delivery.