ABSTRACT The dermal route, a significant pathway for topical and transdermal drug delivery, is not without its challenges. A primary barrier function of skin is attributed to the stratum corneum (SC), which protects us from mechanical insults, ultraviolet light, pathogenic microorganisms, chemical compounds, and other percutaneous penetrants. While skin is an effective barrier against percutaneous absorption of exogenous material, it is also a major route by which they may enter the body. Once absorbed into the skin, penetrants may act locally or enter the circulation to produce systemic effects. Ngo delineates 15 factors that influence the ability of compounds to penetrate the skin, although there are presumably more, demonstrating the complexities of this process. These factors should be considered when designing topical and transdermal drugs, as well as defining toxic potential. Understanding and further elucidating these factors may help to improve drug efficacy and to overcome barriers in clinical care, as well as to improving product safety.
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