EXOSOME-BASED THERAPEUTICS AND DRUG DELIVERY SYSTEMS: ISOLATION, ENGINEERING, AND CLINICAL TRANSLATION

Abstract

Exosomes are small extracellular vesicles (30–150 nm) secreted by most cell types, carrying proteins, lipids, and nucleic acids that mediate intercellular communication. Their natural biocompatibility, low immunogenicity, ability to cross biological barriers, and intrinsic targeting properties have attracted intense interest for therapeutic and drug delivery applications. Exosomes can be loaded with small molecules, proteins, or nucleic acids and engineered to display targeting ligands, enabling precise delivery to specific tissues or cells. This review critically examines the current state of exosome-based therapeutics, focusing on isolation methods, engineering strategies, and clinical translation through early 2024. Isolation techniques include ultracentrifugation, size-exclusion chromatography, and microfluidic approaches, each with trade-offs in purity, yield, and scalability. Engineering strategies encompass cargo loading via electroporation, sonication, or co-incubation, and surface modification using chemical conjugation or genetic fusion. Preclinical studies have demonstrated therapeutic potential in oncology, cardiovascular disease, neurological disorders, and regenerative medicine. Several clinical trials are evaluating exosomes, including mesenchymal stem cell-derived exosomes for COVID-19 and graft-versus-host disease, and plant-derived exosomes for drug delivery. Challenges include heterogeneity, scalable manufacturing, batch-to-batch reproducibility, regulatory classification, and biodistribution. Future directions include standardized isolation and characterization, improved cargo loading efficiency, and development of allogeneic off-the-shelf products. Exosome-based therapeutics hold promise, but rigorous quality control and clinical evidence are required.