Transdermal drug delivery helps to circumvent the first-pass effect of drugs and to avoid drug-induced gastrointestinal tract irritation, compared with oral administration. With the extensive application of ethosomes in transdermal delivery, the shortages of them have been noticed continuously. Due to the high concentration of volatile ethanol in ethosomes,
there are problems of drug leakage, system instability, and ethosome-induced skin irritation. Thus, there is a growing interest in the development of new generations of ethosomal systems. Functionalized ethosomes have the advantages of increased stability, improved transdermal performances, an extended prolonged drug release profile and site-specific delivery,
due to their functional materials. To understand comprehensively understand this novel carrier, this review summarizes the
properties of functionalized ethosomes, their mechanism through the skin and their modifications with different materials,
validating their potential as promising transdermal drug delivery carriers. Although functionalized ethosomes have presented a greater role for enhanced topical delivery, challenges regarding their design and future perspectives are also discussed.