Drug-Loaded Extracellular Vesicle-Based Drug Delivery: Advances, Loading Strategies, Therapeutic Applications, and Clinical Challenges

Extracellular vesicle (EV)-based drug delivery systems are gaining attention due to their biocompatibility and ability to cross biological barriers. This review analyzed 65 studies and two clinical trials from 2020 to 2025, focusing on EV sources, loading strategies, and therapeutic applications. Human mesenchymal stem cell-derived EVs are prevalent in oncology, while plant-derived EVs are used in non-oncology applications. Anti-cancer drugs like doxorubicin are commonly loaded into EVs. Despite promising therapeutic benefits and safety in clinical trials, challenges such as variability in isolation methods, production scalability, and safety evaluation hinder clinical translation. Standardization and large-scale studies are needed to advance EV-based therapeutics. Notably, baricitinib-loaded EVs showed potential in reducing inflammation and promoting hair regrowth in alopecia areata mouse models, highlighting the potential of EVs in targeted drug delivery.