Table 5.
Progress in EV drugs development
| Stage | Progress Highlights | Technological advances and considerations | Key challenges |
|---|---|---|---|
| Upstream production | Large-scale culture of EV-producing cells |
- Serum-free media reduced contamination and enhanced yields - 3D culture systems (e.g., microcarriers) better mimic in vivo conditions and scale up - cGMP-compliant scalable processes (8–10 L batches) in development |
- Limited scale-up beyond pilot scale - Variable EVs yield and quality depending on media and culture system |
| Downstream purification | EVs separation from complex supernatant |
- Differential and density gradient centrifugation - Chromatography (gel filtration, ion exchange, affinity) - Ultrafiltration, size exclusion chromatography - Microfluidics, affinity capture (emerging) |
- Low yield and recovery - EVs damage or loss during processing - Purity inconsistency and batch variability |
| Finished product formulation | Long-term stability of EVs |
- Conventional storage in PBS at –80°C - Lyophilization improved room temperature storage - Excipient (e.g., sucrose, trehalose, albumin)-stabilized EVs - New drying methods: continuous, microwave-assisted, thin-film freeze-drying |
- EVs degradation over time - Structure disrupted during lyophilization - Lack of mature formulations |
| Dosage form development | EVs delivery adapted for diverse indications |
- Injectable solutions - Gels and aerosols under exploration |
- Need for optimal delivery mode per indication |
EV extracellular vesicle, EVs extracellular vesicles