Ke Li, Bo Yan, Zhibo Cao, Rongrong Lu, Guotai Wu, Yang Hai
The human skin, specifically the stratum corneum (SC), remains a formidable barrier to the delivery of therapeutic agents. Nearly 80% of new drug candidates exhibit poor solubility or low permeability, necessitating the development of novel delivery vehicles. Therapeutic deep eutectic solvents (TheDES) have emerged as a "green," multifunctional solution capable of significantly enhancing the solubility and transdermal flux of active pharmaceutical ingredients (APIs). This review discusses the physicochemical fundamentals of TheDES, mechanisms of permeation enhancement-including the newly identified "lipid exchange" effect-and the transition from liquid solvents to advanced dosage forms such as eutectogels and nanoemulsions. Current therapeutic applications in pain management, infectious diseases, and chronic conditions are highlighted, alongside critical assessments of dermatological safety and future directions in computational modeling.