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 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.