Pharmacokinetics and biodistribution of extracellular vesicles administered intravenously and intranasally to Macaca nemestrina
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 an...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023
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| Online Access: | https://hdl.handle.net/1721.1/147893 |
| _version_ | 1826197244306522112 |
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| author | Driedonks, Tom Jiang, Linglei Carlson, Bess Han, Zheng Liu, Guanshu Queen, Suzanne E Shirk, Erin N Gololobova, Olesia Liao, Zhaohao Nyberg, Lyle H Lima, Gabriela Paniushkina, Liliia Garcia-Contreras, Marta Schonvisky, Kayla Castell, Natalie Stover, Mitchel Guerrero-Martin, Selena Richardson, Riley Smith, Barbara Machairaki, Vasiliki Lai, Charles P Izzi, Jessica M Hutchinson, Eric K Pate, Kelly AM Witwer, Kenneth W |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Driedonks, Tom Jiang, Linglei Carlson, Bess Han, Zheng Liu, Guanshu Queen, Suzanne E Shirk, Erin N Gololobova, Olesia Liao, Zhaohao Nyberg, Lyle H Lima, Gabriela Paniushkina, Liliia Garcia-Contreras, Marta Schonvisky, Kayla Castell, Natalie Stover, Mitchel Guerrero-Martin, Selena Richardson, Riley Smith, Barbara Machairaki, Vasiliki Lai, Charles P Izzi, Jessica M Hutchinson, Eric K Pate, Kelly AM Witwer, Kenneth W |
| author_sort | Driedonks, Tom |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T10:44:44Z |
| format | Article |
| id | mit-1721.1/147893 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:44:44Z |
| publishDate | 2023 |
| publisher | Wiley |
| record_format | dspace |
| spelling | mit-1721.1/1478932023-02-07T03:37:42Z Pharmacokinetics and biodistribution of extracellular vesicles administered intravenously and intranasally to Macaca nemestrina Driedonks, Tom Jiang, Linglei Carlson, Bess Han, Zheng Liu, Guanshu Queen, Suzanne E Shirk, Erin N Gololobova, Olesia Liao, Zhaohao Nyberg, Lyle H Lima, Gabriela Paniushkina, Liliia Garcia-Contreras, Marta Schonvisky, Kayla Castell, Natalie Stover, Mitchel Guerrero-Martin, Selena Richardson, Riley Smith, Barbara Machairaki, Vasiliki Lai, Charles P Izzi, Jessica M Hutchinson, Eric K Pate, Kelly AM Witwer, Kenneth W Massachusetts Institute of Technology. Department of Biological Engineering 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. 2023-02-06T18:20:01Z 2023-02-06T18:20:01Z 2022 2023-02-06T18:05:59Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/147893 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). en 10.1002/JEX2.59 Journal of Extracellular Biology Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Wiley Wiley |
| spellingShingle | Driedonks, Tom Jiang, Linglei Carlson, Bess Han, Zheng Liu, Guanshu Queen, Suzanne E Shirk, Erin N Gololobova, Olesia Liao, Zhaohao Nyberg, Lyle H Lima, Gabriela Paniushkina, Liliia Garcia-Contreras, Marta Schonvisky, Kayla Castell, Natalie Stover, Mitchel Guerrero-Martin, Selena Richardson, Riley Smith, Barbara Machairaki, Vasiliki Lai, Charles P Izzi, Jessica M Hutchinson, Eric K Pate, Kelly AM Witwer, Kenneth W Pharmacokinetics and biodistribution of extracellular vesicles administered intravenously and intranasally to Macaca nemestrina |
| title | Pharmacokinetics and biodistribution of extracellular vesicles administered intravenously and intranasally to Macaca nemestrina |
| title_full | Pharmacokinetics and biodistribution of extracellular vesicles administered intravenously and intranasally to Macaca nemestrina |
| title_fullStr | Pharmacokinetics and biodistribution of extracellular vesicles administered intravenously and intranasally to Macaca nemestrina |
| title_full_unstemmed | Pharmacokinetics and biodistribution of extracellular vesicles administered intravenously and intranasally to Macaca nemestrina |
| title_short | Pharmacokinetics and biodistribution of extracellular vesicles administered intravenously and intranasally to Macaca nemestrina |
| title_sort | pharmacokinetics and biodistribution of extracellular vesicles administered intravenously and intranasally to macaca nemestrina |
| url | https://hdl.handle.net/1721.1/147893 |
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