Alternative biological sources for extracellular vesicles production and purification strategies for process scale-up

Extracellular vesicles (EVs) are phospholipidic bi-layer enclosed nanoparticles secreted naturally by all cell types. They are attracting increasing attention in the fields of nanomedicine, nutraceutics and cosmetics as biocom-patible carriers for drug delivery, with intrinsic properties beneficial to human health. Scientific work now fo-cuses on developing techniques for isolating EVs that can translate into industrial-scale production and meet rigorous clinical requirements. The science of EVs is ongoing, and many pitfalls must be addressed, such as the requirement for standard, reproducible, inexpensive, and Good Manufacturing Practices (GMP) adherent EV processing techniques. Researchers are exploring the use of alternative sources to EVs derived from mammalian cultures, such as plant EVs, as well as the use of bacteria, algae and milk. Regarding the downstream processing of EVs, many alternative techniques to the ultracentrifugation (UC) protocols most commonly used in the lab-oratory are emerging. In the context of process scale-up, membrane-based processes for isolation and purification of EVs are the most promising, either as stand-alone processes or in combination with chromatographic tech-niques. This review discusses current trends on EVs source selection and EVs downstream processing techniques, with a focus on plant-derived EVs and membrane-based techniques for EVs enrichment.

Automated summary

Extracellular vesicles (EVs) are naturally secreted nanoparticles by all cell types, and they are being researched as biocompatible carriers for drug delivery due to their beneficial properties. The scientific focus is on developing techniques for isolating EVs that can be produced on an industrial scale and meet clinical requirements. Researchers are exploring alternative sources of EVs, such as plant EVs, and alternative techniques for EVs processing, including membrane-based processes for isolation and purification.