Liraglutide‐Loaded Milk Exosomes Lower Blood Glucose When Given by Sublingual Route

Abstract Bovine milk is rich in extracellular vesicles (mEVs) which have been suggested as a possible drug delivery vehicle with oral bioavailability. As the digestive fluids contain many lipid‐ and protein‐degrading enzymes, we explored whether mEVs given sublingually could be taken up systemically. mEVs were isolated using three different protocols, which were 120 nm in diameter and carried bovine CD81. Fluorescently stained mEVs given by sublingual route were detected in the circulation, whereas mEVs given by gavage were detected at 2‐Log lower concentrations. As proof of the concept, we loaded mEVs with the antidiabetic drug Liraglutide (LRT‐EV), which reduced blood glucose levels when given by the sublingual route but showed no efficacy via gavage. This study suggests that mEV may be an efficient delivery vehicle for drugs that are not orally bioavailable, and LRT‐loaded EVs have the potential as the next‐generation drug delivery platform for the treatment of chronic diseases, including diabetes.