Evidence map›Paper›PMID 36591537›Full record

ArticleJournal of extracellular biology2022

Pharmacokinetics and biodistribution of extracellular vesicles administered intravenously and intranasally to

Tom Driedonks, Linglei Jiang, Bess Carlson, Zheng Han, Guanshu Liu, Suzanne E Queen, Erin N Shirk, Olesia Gololobova, Zhaohao Liao, Lyle H Nyberg and 15 more

Erratum issuedOpen access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of extracellular biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 137 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
137citing papers in PubMed, 3 pooled it
13.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

137 citing papers in PubMed, 3 syntheses or guidelines pooled it, 166 citations in OpenAlex.

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77 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors at 3 institutions in 2 countries.

Tom DriedonksDept. Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, US.
Linglei JiangDept. Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, US.
Bess CarlsonDept. Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, US.
Zheng HanRussell H. Morgan Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, US.
Guanshu LiuRussell H. Morgan Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, US.
Suzanne E QueenDept. Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, US.
Erin N ShirkDept. Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, US.
Olesia GololobovaDept. Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, US.
Zhaohao LiaoDept. Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, US.
Lyle H NybergDept. Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, US.
Gabriela LimaDept. Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, US.
Liliia PaniushkinaDept. Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, US.
Marta Garcia-ContrerasDept. Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, US.
Kayla SchonviskyDept. Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, US.
Natalie CastellDept. Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, US.
Mitchel StoverDept. Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, US.
Selena Guerrero-MartinDept. Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, US.
Riley RichardsonDept. Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, US.
Barbara SmithDept. Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, US.
Vasiliki MachairakiThe Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease, Johns Hopkins University School of Medicine, Baltimore, MD, US.
Charles P LaiInstitute of Atomic and Molecular Sciences, Academia Sinica, Taipei, Taiwan.
Jessica M IzziDept. Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, US.
Eric K HutchinsonDept. Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, US.
Kelly A M PateDept. Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, US.
Kenneth W WitwerDept. Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, US.
Johns Hopkins University · USKennedy Krieger Institute · USInstitute of Atomic and Molecular Sciences, Academia Sinica · TW

Funding

Viral Testing CoreU42OD013117 · OD · JOHNS HOPKINS UNIVERSITY · PI JOSEPH L MANKOWSKI · 2017 to 2026
$10.9M
Training Veterinarians for Careers in Biomedical ResearchT32OD011089 · OD · JOHNS HOPKINS UNIVERSITY · PI JOSEPH L MANKOWSKI · 2012 to 2026
$6.7M
Next-generation extracellular vesicle biologics to target central nervous system and peripheral reservoirs of HIVR01AI144997 · NIAID · JOHNS HOPKINS UNIVERSITY · PI RAMRATNAM, BHARAT, WITWER, KENNETH W · 2019 to 2023
$4.0M
Extracellular Vesicle and Extracellular RNA Biomarkers of HIV-1 Central Nervous System Pathogenesis and Cigarette UseR01DA047807 · NIDA · JOHNS HOPKINS UNIVERSITY · PI WITWER, KENNETH W · 2018 to 2022
$3.7M
Novel Approaches to Capture, Sorting, and Characterization of CNS-Origin Extracellular VesiclesR33MH118164 · NIMH · JOHNS HOPKINS UNIVERSITY · PI MACHAIRAKI, VASILIKI, WITWER, KENNETH W · 2020 to 2022
$2.2M
Novel Separation Methods for exRNA Carriers: Extracellular Vesicles, Lipoprotein Particles, and Protein AggregatesUH3CA241694 · NCI · JOHNS HOPKINS UNIVERSITY · PI WITWER, KENNETH W · 2021 to 2022
$1.1M
Novel Separation Methods for exRNA Carriers: Extracellular Vesicles, Lipoprotein Particles, and Protein AggregatesUG3CA241694 · NCI · JOHNS HOPKINS UNIVERSITY · PI WITWER, KENNETH W · 2019 to 2020
$941k
Novel Approaches to Capture, Sorting, and Characterization of CNS-Origin Extracellular VesiclesR21MH118164 · NIMH · JOHNS HOPKINS UNIVERSITY · PI MACHAIRAKI, VASILIKI, WITWER, KENNETH W · 2018 to 2019
$471k
NCI NIH HHS UG3 CA241694NCI NIH HHS UH3 CA241694NIAID NIH HHS R01 AI144997NIDA NIH HHS R01 DA047807NIH HHS T32 OD011089NIH HHS U42 OD013117NIMH NIH HHS R21 MH118164NIMH NIH HHS R33 MH118164
6 · The paper itself

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.

Indexed as

biodistributiondrug deliveryextracellular vesiclesmacaquesnanomedicinepharmacokineticstherapeutics

Identifiers

PMID36591537
PMCPMC9799283
OpenAlexW4304183732

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.