Bovine milk- and colostrum-derived exosomes carry a variety of endogenous cargos, including proteins, lipids, and nucleic acids. The figure shows that small molecules associate with exosomes by interacting with the hydrophobic domains of proteins on the vesicle surface. Conversely, loading of negatively charged biologics requires a polycationic mediator in the form of polyethyleneimine (PEI) to first condense and encapsulate the nucleic acids, and then associate with the negatively charged surface areas of the exosome particles, forming the EPM-siRNA.