Fenugreek-derived exosome-like nanovesicles containing bioavailable phytoferritin for the management of iron deficiency anemia

Iron deficiency anemia (IDA) affects 50 % to 60 % of Indian women. Though, iron supplements are often pre­
scribed, poor bioavailability and side effects limits their use. Phytoferritin, a nanocage containing ~4500 ferric
atoms, has been proposed as an alternative, though it’s in vivo bioavailability remains debatable. Plant-derived
nanovesicles (PDNVs) are exosome-mimetic vesicles naturally derived from plants. Herein, we demonstrate the
presence of phytoferritin nanocages in fenugreek seed PDNVs (FGDNVs). Unlike native pea ferritin (PF),
FGDNVs-resident phytoferritin was stable in simulated gastrointestinal digestion. FGDNVs possessed better in
vitro bioavailability in Caco-2 and RAW264.7 cells compared to PF. In IDA rats, oral administration of FGDNVs,
but not PF, led to stable delivery of phytoferritin in the stomach, duodenum and jejunum tissues. Notably,
FGDNVs containing one tenth of recommended dietary allowance of iron, rescued ID and restored hematological
parameters. Thus, FGDNVs represent a natural iron nano-formulation for safe and efficient therapeutics for IDA.