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Zebrafish as an early stage screening tool to study the systemic circulation of nanoparticulate drug delivery systems in vivo

Sieber, Sandro and Grossen, Philip and Detampel, Pascal and Siegfried, Salome and Witigmann, Dominik and Huwyler, Jörg. (2017) Zebrafish as an early stage screening tool to study the systemic circulation of nanoparticulate drug delivery systems in vivo. Journal of Controlled Release, 264. pp. 180-191.

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Official URL: http://edoc.unibas.ch/56086/

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Abstract

Nanomedicines have gained much attention for the delivery of small molecules or nucleic acids as treatment options for many diseases. However, the transfer from experimental systems to in vivo applications remains a challenge since it is difficult to assess their circulation behavior in the body at an early stage of drug discovery. Thus, innovative and improved concepts are urgently needed to overcome this issue and to close the gap between empiric nanoparticle design, in vitro assessment, and first in vivo experiments using rodent animal models. This study was focused on the zebrafish as a vertebrate screening model to assess the circulation in blood and extravasation behavior of nanoparticulate drug delivery systems in vivo. To validate this novel approach, monodisperse preparations of fluorescently labeled liposomes with similar size and zeta potential were injected into transgenic zebrafish lines expressing green fluorescent protein in their vasculature. Phosphatidylcholine-based lipids differed by fatty acid chain length and saturation. Circulation behavior and vascular distribution pattern were evaluated qualitatively and semi-quantitatively using image analysis. Liposomes composed of lipids with lower transition temperature (< 28  °C) as well as PEGylated liposomes showed longer circulation times and extravasation. In contrast, liposomes composed of lipids with transition temperatures > 28  °C bound to venous parts of the vasculature. This circulation patterns in the zebrafish model did correlate with published and experimental pharmacokinetic data from mice and rats. Our findings indicate that the zebrafish model is a useful vertebrate screening tool for nanoparticulate drug delivery systems to predict their in vivo circulation behavior with respect to systemic circulation time and exposure.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmaceutical Technology (Huwyler)
UniBasel Contributors:Huwyler, Jörg and Grossen, Philip and Detampel, Pascal and Sieber, Sandro
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Elsevier
ISSN:0168-3659
e-ISSN:1873-4995
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:23 Oct 2017 10:07
Deposited On:23 Oct 2017 10:07

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