Surfactants as transdermal penetration enhancers: structure, mechanism, and application

Surfactants, owing to their unique physicochemical properties, are capable of significantly modifying the skin's barrier function, thereby enhancing the transdermal permeability of active compounds. This review delves into the utilization of cationic, anionic, zwitterionic, nonionic surfactants, as well as biosurfactants and mixed surfactants systems, in facilitating transdermal penetration. Beyond the influence of the headgroup, several other key factors affecting enhancement efficacy are discussed, including hydrophobic chain length, molecular conformation, chirality, and the formation of various assembly carriers (e.g., micelles, vesicles, and microemulsions). Surfactants exert their transdermal enhancement effects through multiple mechanisms, such as modifying the protein structure of the stratum corneum, disrupting the lipid matrix, and increasing the solubility and diffusivity of active compounds. In addition, this review highlights the broad applications of surfactants in both transdermal drug and cosmeceutical delivery, while also addressing safety concerns such as irritation and cytotoxicity. Finally, it outlines the current challenges and future directions in the development of surfactant-based transdermal delivery systems. This work aims to provide insightful guidance on the rational design and selection of surfactants to achieve targeted and efficient transdermal permeation.