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: Postprint online available 10/2020
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Cellular vesicles: New insights in engineering methods, interaction with cells and potential for brain targeting.
J. Pharmacol. Exp. Ther. 370, 772-785 (2019)
Publ. Version/Full Text
DOI
Cellular vesicles (CVs) have been proposed as alternatives to exosomes for targeted drug delivery. CVs, prepared from human embryonic kidney 293 cells (HEK-293), C57BL/6 mouse B16F10 skin melanoma cells (B16F10), and immortalized human cerebral microvascular endothelial cells (hCMEC/D3) by liposome technology methods, were characterized for morphology, cytotoxicity, and cell uptake properties. CV brain-targeting potential was evaluated in vitro on the hCMEC/D3 blood-brain barrier (BBB) model, and in vivo/ex vivo. CV sizes were between 135 and 285 nm, and the ζ-potential was negative. The dehydration-rehydration method conferred highest calcein loading and latency to CVs compared with other methods. The increased calcein leakage from CVs when compared with liposomes indicated their poor integrity, which was increased by pegylation. The in vivo results confirmed lower liver uptake by PEG-CVs (compared with nonpegylated) proving that the calcein integrity test is useful for prediction of CV biodistribution, as used for liposomes. The cell uptake of homologous origin CVs was not always higher compared with that of non-homologous. Nevertheless, CVs from hCMEC/D3 demonstrated the highest BBB permeability (in vitro) compared with OX-26 targeted liposomes, and brain localization (in vivo). CVs from hCMEC/D3 cells grown in different media demonstrated decreased interaction with brain cells and brain localization. Significant differences in proteome of the two latter CV types were identified by proteomics, suggesting a potential methodology for identification of organotropism-determining CV components.
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Publication type
Article: Journal article
Document type
Scientific Article
ISSN (print) / ISBN
0022-3565
e-ISSN
1521-0103
Quellenangaben
Volume: 370,
Issue: 3,
Pages: 772-785
Publisher
American Society for Pharmacology and Experimental Therapeutics (ASPET)
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Lung Health and Immunity (LHI)