Natural Ingredients of Transdermal Drug Delivery Systems as Permeation Enhancers of Active Substances through the Stratum Corneum

[Image: see text] In recent years, significant progress has been made in transdermal drug delivery systems, but there is still a search for enhancers that can improve the absorption of active substances through the stratum corneum. Although permeation enhancers have been described in the scientific literature, the use of naturally occurring substances in this role is still of particular interest, because they can offer a high level of safety of use, with a low risk of skin irritation, and high efficiency. In addition, these ingredients are biodegradable, easily available, and widely accepted by consumers due to the growing trust in natural compounds. This article provides information on the role of naturally derived compounds in transdermal drug delivery systems that help them penetrate the skin. The work focuses on the components found in the stratum corneum such as sterols, ceramides, oleic acid, and urea. Penetration enhancers found in nature, mainly in plants, such as terpenes, polysaccharides, and fatty acids have also been described. The mechanism of action of permeation enhancers in the stratum corneum is discussed, and information on the methods of assessing their penetration efficiency is provided. Our review mainly covers original papers from 2017 to 2022, supplemented with review papers, and then older publications used to supplement or verify the data. The use of natural penetration enhancers has been shown to increase the transport of active ingredients through the stratum corneum and can compete with synthetic counterparts.