Challenges in the development and establishment of exosome-based drug delivery systems

Exosomes are extracellular vesicles released from cells and are characterized by a lipid bilayer membrane encapsulating a variety of biological molecules such as nucleic acids or proteins within the lumen or the lipid-bilayer. Under physiological environments, exosomes mediate cell-to-cell communication and cargo transport. Therefore, exosomes have been explored as drug delivery vehicles for improving therapeutic outcomes. Although recent studies have demonstrated promising advances with exosome-based drug delivery systems, several challenges severely hinder further development of exosomes for clinical applications. This review summarizes and emphasizes some of the technical challenges related to the isolation, characterization, and stability testing of exosomes. More importantly, challenges related specifically to the application of exosomes for drug delivery such as cell-uptake, drug loading, drug release, and in vivo distribution will be examined in this article.