Pharmacokinetics and biodistribution of extracellular vesicles administered intravenously and intranasally to Macaca nemestrina
Name
J of Extracellular Bio - 2022 - Driedonks - Pharmacokinetics and biodistribution of extracellular vesicles administered.pdf
Description
Published version
Size
2.12 MB
Format
Adobe PDF
Checksum (MD5)
c67393e43f849e5b0ba1e96de325d1c9
Author(s)
Driedonks, Tom
Jiang, Linglei
Carlson, Bess
Han, Zheng
Liu, Guanshu
Queen, Suzanne E
Shirk, Erin N
Gololobova, Olesia
Liao, Zhaohao
Nyberg, Lyle H
Date Issued
2022
Journal
Journal of Extracellular Biology
Publisher
Wiley
Citation
Driedonks, Tom, Jiang, Linglei, Carlson, Bess, Han, Zheng, Liu, Guanshu et al. 2022. "Pharmacokinetics and biodistribution of extracellular vesicles administered intravenously and intranasally to Macaca nemestrina." Journal of Extracellular Biology, 1 (10).
Version
Final published version
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 Expi293F-derived EVs labelled with a highly sensitive nanoluciferase reporter (palmGRET) in a non-human primate model (Macaca nemestrina), comparing intravenous (IV) and intranasal (IN) administration over a 125-fold 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 (CSF) after 30-60 minutes. EV association with PBMCs, especially B-cells, was observed as early as one minute post-administration. EVs were detected in liver and spleen within one hour 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 EV-based therapeutics. We hope that our findings from this baseline study in macaques will help to inform future research and therapeutic development of EVs.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1002/JEX2.59
