Liposome-Mediated Drug Delivery in Larval Zebrafish to Manipulate Macrophage Function.

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dc.contributor.author Wu, Zimei en
dc.contributor.author Koh, Ben en
dc.contributor.author Lawrence, Lisa M en
dc.contributor.author Kanamala, Manju en
dc.contributor.author Pool, Bregtina en
dc.contributor.author Svirskis, Darren en
dc.contributor.author Dalbeth, Nicola en
dc.contributor.author Astin, Jonathan en
dc.contributor.author Crosier, Kathryn en
dc.contributor.author Crosier, Philip en
dc.contributor.author Hall, Christopher en
dc.date.accessioned 2019-06-19T21:36:20Z en
dc.date.issued 2019-04 en
dc.identifier.issn 1545-8547 en
dc.identifier.uri http://hdl.handle.net/2292/47243 en
dc.description.abstract Chemical interventions are regularly used to examine and manipulate macrophage function in larval zebrafish. Given chemicals are typically administered by simple immersion or injection, it is not possible to resolve whether their impact on macrophage function is direct or indirect. Liposomes provide an attractive strategy to target drugs to specific cellular compartments, including macrophages. As an example, injecting liposomal clodronate into animal models, including zebrafish, is routinely used to deliver toxic levels of clodronate specifically to macrophages for targeted cell ablation. Here we show that liposomes can also target the delivery of drugs to zebrafish macrophages to selectively manipulate their function. We utilized the drugs etomoxir (a fatty acid oxidation inhibitor) and MitoTEMPO (a scavenger of mitochondrial reactive oxygen species [mROS]), that we have previously shown, through free drug delivery, suppress monosodium urate (MSU) crystal-driven macrophage activation. We generated poloxamer 188 modified liposomes that were readily phagocytosed by macrophages, but not by neutrophils. Loading these liposomes with etomoxir or MitoTEMPO and injecting into larvae suppressed macrophage activation in response to MSU crystals, as evidenced by proinflammatory cytokine expression and macrophage-driven neutrophil recruitment. This work reveals the utility of packaging drugs into liposomes as a strategy to selectively manipulate macrophage function. en
dc.format.medium Print-Electronic en
dc.language eng en
dc.relation.ispartofseries Zebrafish en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.subject Macrophages en
dc.subject Animals en
dc.subject Zebrafish en
dc.subject Epoxy Compounds en
dc.subject Organophosphorus Compounds en
dc.subject Piperidines en
dc.subject Liposomes en
dc.subject Enzyme Inhibitors en
dc.subject Antioxidants en
dc.subject Drug Delivery Systems en
dc.subject Models, Animal en
dc.title Liposome-Mediated Drug Delivery in Larval Zebrafish to Manipulate Macrophage Function. en
dc.type Journal Article en
dc.identifier.doi 10.1089/zeb.2018.1681 en
pubs.issue 2 en
pubs.begin-page 171 en
pubs.volume 16 en
dc.rights.holder Copyright: The author en
pubs.end-page 181 en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/RestrictedAccess en
pubs.subtype Journal Article en
pubs.elements-id 767999 en
pubs.org-id Medical and Health Sciences en
pubs.org-id Medical Sciences en
pubs.org-id Molecular Medicine en
pubs.org-id Pharmacy en
pubs.org-id School of Medicine en
pubs.org-id Medicine Department en
pubs.org-id Science en
pubs.org-id Science Research en
pubs.org-id Maurice Wilkins Centre (2010-2014) en
dc.identifier.eissn 1557-8542 en
pubs.record-created-at-source-date 2019-02-07 en
pubs.dimensions-id 30724716 en


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