Non-invasive administration of exosomes.

Exosomes, as naturally derived extracellular vesicles, have emerged as promising therapeutic carriers due to their intrinsic biocompatibility, low immunogenicity, and ability to facilitate intercellular communication. In recent years, the non-invasive administration of exosomes has gained increasing attention as a strategy to enhance patient compliance and improve drug delivery efficiency while circumventing the limitations associated with traditional invasive routes. This review provides a comprehensive overview of the non-invasive delivery of exosome-based therapeutics, spanning oral, intranasal, inhalation, ocular, and transdermal administration. Moreover, we discuss underexplored pathways with unique anatomical and physiological advantages for systemic and local therapy, including sublingual, otic, rectal, and vaginal delivery. Each administration route will outline the key anatomic and biological barriers that exosomes must overcome, along with commonly employed strategies to address them. We further explore the therapeutic potential of non-invasive exosome delivery across various diseases, highlighting the advantages and limitations of each approach. Finally, we discuss the current challenges in translating non-invasive exosome delivery into clinical practice and propose future directions to advance this goal.