Liposome-Mediated Drug Delivery in Larval Zebrafish to Manipulate Macrophage Function
| Autor: | Nicola Dalbeth, Lisa M. Lawrence, Bregina Pool, Christopher J. Hall, Jonathan W. Astin, Manju Kanamala, Kathryn E. Crosier, Zimei Wu, Ben Koh, Philip S. Crosier, Darren Svirskis |
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| Rok vydání: | 2019 |
| Předmět: |
Cell
Antioxidants Proinflammatory cytokine 03 medical and health sciences chemistry.chemical_compound Drug Delivery Systems Organophosphorus Compounds 0302 clinical medicine Piperidines medicine Animals Enzyme Inhibitors Zebrafish Cellular compartment 030304 developmental biology chemistry.chemical_classification 0303 health sciences Reactive oxygen species Liposome biology Macrophages biology.organism_classification Cell biology medicine.anatomical_structure chemistry Liposomes Models Animal Drug delivery Epoxy Compounds Animal Science and Zoology 030217 neurology & neurosurgery Etomoxir Developmental Biology |
| Zdroj: | Zebrafish. 16:171-181 |
| ISSN: | 1557-8542 1545-8547 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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