Plant-derived extracellular vesicles as oral drug delivery carriers

Oral administration is one of the most convenient and widely utilized methods of drug administration. However, many drugs were difficult to be administered orally due to their poor oral bioavailability. Designing a safe and effective oral drug delivery system is one of the basic strategies to overcome the poor oral bioavailability. Plant-derived extracellular vesicles (PDEVs) were found in a variety of plants and have similar physical and chemical properties to mammalian EVs. It has been proved that PDEVs can effectively encapsulate hydrophilic and hydrophobic drugs, remain stable in harsh gastrointestinal environments, and cross biological barriers to reach target tissues. Furthermore, the biological activity of PDEVs enables it to play a synergistic therapeutic role with drugs. In addition, the safety and high yield of PDEVs indicate their potential as oral drug carriers. In this review, we introduce the biogenesis, isolation, characterization and drug delivery methods of PDEVs, describe their stability, transport, delivery and therapeutic applications. Finally, the potential and challenges of PDEVs as drug carriers are discussed.