Spatiotemporal imaging and pharmacokinetics of fluorescent compounds in zebrafish eleuthero-embryos after different routes of administration

被引：13

作者：

Guarin, Marlly ^{[1
]}

Faelens, Ruben ^{[4
]}

Giusti, Arianna ^{[1
]}

De Croze, Noemie ^{[2
]}

Leonard, Marc ^{[2
]}

Cabooter, Deirdre ^{[3
]}

Annaert, Pieter ^{[4
]}

de Witte, Peter ^{[1
]}

Ny, Annelii ^{[1
]}

机构：

[1] Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Lab Mol Biodiscovery, Leuven, Belgium

[2] LOreal Res & Innovat, Aulnay Sous Bois, France

[3] Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Pharmaceut Anal, Leuven, Belgium

[4] Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Drug Delivery & Disposit, Leuven, Belgium

来源：

SCIENTIFIC REPORTS | 2021年 / 11卷 / 01期

基金：

欧盟地平线“2020”;

关键词：

BLOOD-BRAIN-BARRIER; INJECTION; REVEALS; SYSTEMS; FISH;

D O I：

10.1038/s41598-021-91612-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Zebrafish (Danio rerio) is increasingly used to assess the pharmacological activity and toxicity of compounds. The spatiotemporal distribution of seven fluorescent alkyne compounds was examined during 48 h after immersion (10 mu M) or microinjection (2 mg/kg) in the pericardial cavity (PC), intraperitoneally (IP) and yolk sac (IY) of 3 dpf zebrafish eleuthero-embryos. By modelling the fluorescence of whole-body contours present in fluorescence images, the main pharmacokinetic (PK) parameter values of the compounds were determined. It was demonstrated that especially in case of short incubations (1-3 h) immersion can result in limited intrabody exposure to compounds. In this case, PC and IP microinjections represent excellent alternatives. Significantly, IY microinjections did not result in a suitable intrabody distribution of the compounds. Performing a QSPkR (quantitative structure-pharmacokinetic relationship) analysis, LogD was identified as the only molecular descriptor that explains the final uptake of the selected compounds. It was also shown that combined administration of compounds (immersion and microinjection) provides a more stable intrabody exposure, at least in case of a prolonged immersion and compounds with LogD value>1. These results will help reduce the risk of false negative results and can offer an invaluable input for future translational research and safety assessment applications.

引用

页数：15