1 research outputs found
Pharmacokinetics and biodistribution of extracellular vesicles administered intravenously and intranasally to Macaca nemestrina
Abstract Extracellular vesicles (EVs) have potential in disease treatment since they can be loaded with therapeutic molecules and engineered for retention by specific tissues. However, questions remain on optimal dosing, administration and pharmacokinetics. Previous studies have addressed biodistribution and pharmacokinetics in rodents, but little evidence is available for larger animals. Here, we investigated the pharmacokinetics and biodistribution of Expi293Fâderived EVs labelled with a highly sensitive nanoluciferase reporter (palmGRET) in a nonâhuman primate model (Macaca nemestrina), comparing intravenous (IV) and intranasal (IN) administration over a 125âfold dose range. We report that EVs administered IV had longer circulation times in plasma than previously reported in mice and were detectable in cerebrospinal fluid after 30â60 min. EV association with peripheral blood mononuclear cells, especially Bâcells, was observed as early as 1âmin postâadministration. EVs were detected in liver and spleen within 1 h of IV administration. However, IN delivery was minimal, suggesting that pretreatment approaches may be needed in large animals. Furthermore, EV circulation times strongly decreased after repeated IV administration, possibly due to immune responses and with clear implications for xenogeneic EVâbased therapeutics. We hope that our findings from this baseline study in macaques will help to inform future research and therapeutic development of EVs