Applications of extracellular vesicles as a drug-delivery system for chronic respiratory diseases

Tremendous advancements in nanotechnology have contributed to the development of 'smart' nanoparticle systems that can effectively transport a drug to the desired site of release. Ideally, the nanoparticles carrying the drug cargo are stable during their transit in circulation, deliver to the target site without interacting with nontarget tissues, and enhance the drug lifespan in circulation for sustained or extended release, if necessary. Nanocarriers such as liposomes, which are lipid-based, can stably incorporate hydrophilic, lipophilic or amphiphilic drug molecules and can overcome the natural cell membrane barrier by readily fusing with cell membrane to release drug molecules inside the cells. Drug-loaded liposomes, containing doxorubicin or paclitaxel, have been used clinically with cellsurface modifications to specifically deliver and release the drug at the target site in response to the external stimuli such as pH, heat, redox potential or unique enzymatic activity of the tissue microenvironment. However, liposomal drug carriers still possess few safety and stability issues, namely rapid clearance via the reticuloendothelial system, toxicity at high doses and host immunogenic responses after repeated administration. Recently, cell-derived extracellular vesicles (EVs) have been investigated as a viable drug-delivery system, which can overcome the many limitations of synthetic liposomal drug formulations.