Biomimetic and Natural Exosomes in Drug Delivery: A Critical Review

Exosomes are biological nanoparticles (30–150 nm) secreted by most eukaryotic cells. They are composed of a lipid bilayer membrane and an inner compartment that stores various cellular components. In recent years, research on exosomes has grown exponentially due to their biocompatibility, low immunogenicity and cytotoxicity, and their permeability to biological barriers. Among the most promising applications of exosomes are their diagnostic and therapeutic potential, the latter being especially relevant due to their ability to act as a vehicle for drugs. Before exosomes can be applied clinically, it is necessary to optimize the isolation of these nanoparticles from various sources, as well as to carry out their physical and biochemical characterization. Furthermore, their ability to encapsulate molecules with therapeutic effects within them must be perfected. To this end, analytical methods are a key tool for developing each of these steps, and it is essential to understand their principles, strengths, and challenges. In addition, it is necessary to overcome limitations such as the availability of safe sources, the scalability of production, the standardization of isolation, purification, and encapsulation, the inherent heterogeneity of exosomes themselves, the prolongation of in vivo lifespan, and the long-term preservation of these nanoparticles. An alternative is the synthesis of exosome-like nanoparticles, which is less complex but more prone to high production and tailored structure and composition. This review addresses the latest advances in drug delivery focused on exosomes and exosome biomimetic nanoparticles, comparing their advantages and drawbacks from a practical perspective.