Exosomes as a next-generation drug delivery system: An update on drug loading approaches, characterization, and clinical application challenges

Exosomes are small nanoparticles secreted by almost all cells and have a well-known role in intercellular communication. They are found in different body fluids and can also be isolated from cell culture media. They contain a natural cargo including various protein and nucleic acid molecules originated from their donor cells. In recent years, exosomes have emerged as a desired drug delivery system. They are believed to provide a targeted delivery of drug molecules, supplemented with their natural function. Furthermore, they have a membranous structure similar to liposomes, and that motivated researchers to apply their previous experience of drug loading into liposomes for exosomes. Herein, we discuss applied methods for the encapsulation of different drugs into exosomes, parameters affecting the incorporation of drug molecules into exosomes, characterization techniques, recent achievements, commercialization challenges and the potential future developments of exosomal drugs. Overall, while the application of exosomes as a drug delivery system is still in its infancy, they are considered to be a new class of natural nanocarriers with great potential for clinical application. Understanding of their key formulation parameters, pharmaceutical properties, in vivo behavior and applicable scale-up production will pave their way to the market. Details of loading methods, characterization and biopharmaceutical properties of drug-incorporated exosomes are presented. Most parameters affecting encapsulation of drugs into exosomes are mentioned to serve as a guide for future studies in this field. Moreover, challenges on the way of exosomes to the market and clinic are described.