The Study of Ginger-Derived Extracellular Vesicles as a Natural Nanoscale Drug Carrier and Their Intestinal Absorption in Rats.

Extracellular vesicles have been widely used in drug delivery systems and clinical studies as a new natural nanoscale drug carrier. Most of these studies focused on the extracellular vesicles from animals, but few involved in the extracellular vesicles from edible plants. This study was the first to explore the potential and value of ginger-derived extracellular vesicles (GDEVs) as drug carrier by using the content ratio method and to further study their intestinal absorption in rats. In this experiment, GDEVs were extracted and purified by ultrahigh-speed centrifugation. GDEVs were saucer-like with a particle size of 70.09±19.24 nm and a zeta potential of -27.70±12.20 mV. In this experiment, high-performance liquid chromatography was used to explore the difference in gingerol content between GDEVs and ginger slices. Under the same mass, the contents of 6-gingerol (6G), 8-gingerol (8G), and 10-gingerol (10G) in GDEVs were 10.21-fold, 22.69-fold, and 32.36-fold of those in ginger slices, respectively. In this experiment, the absorption kinetics and absorption site of GDEVs were investigated using in situ single-pass intestinal perfusion method in rats. GDEVs could be absorbed by the small intestine in the concentration range of 15-60 mg/mL, and the absorption trend of different intestinal segments was duodenum > jejunum > ileum. These results indicated that GDEVs had good loading capacity and significant prospects as a carrier of the drug delivery system. At the same time, combining the oil-water partition coefficient (6G < 8G < 10G) of three gingerol compounds, we speculated that the loading capacity of GDEVs increased with the increase of the lipid solubility of the compounds. This study fully demonstrated the potential and value of ginger-derived extracellular vesicles as natural nanocarrier and provided an important reference for the further application of plant-derived extracellular vesicles in the drug delivery system.