Evaluation of the Percutaneous Absorption of Drug Molecules in Zebrafish

In recent decades, zebrafish (<i>Danio rerio</i>) has become a widely used vertebrate animal model for studying development and human diseases. However, studies on skin medication using zebrafish are rare. Here, we developed a novel protocol for percutaneous absorption of molecules via t...

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Main Authors: Daizo Morikane, Liqing Zang, Norihiro Nishimura
Format: Article
Language:English
Published: MDPI AG 2020-08-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/25/17/3974
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author Daizo Morikane
Liqing Zang
Norihiro Nishimura
author_facet Daizo Morikane
Liqing Zang
Norihiro Nishimura
author_sort Daizo Morikane
collection DOAJ
description In recent decades, zebrafish (<i>Danio rerio</i>) has become a widely used vertebrate animal model for studying development and human diseases. However, studies on skin medication using zebrafish are rare. Here, we developed a novel protocol for percutaneous absorption of molecules via the zebrafish tail skin, by applying a liquid solution directly, or using a filter paper imbibed with a chemical solution (coating). Human skin is capable of absorbing felbinac and loxoprofen sodium hydrate (LSH), but not glycyrrhetinic acid (GA) and terbinafine hydrochloride (TH). To evaluate the possibility and the quality of transdermal absorption in zebrafish, we transdermally administered these four drugs to zebrafish. Pharmacokinetics showed that felbinac was present in the blood of zebrafish subjected to all administration methods. Felbinac blood concentrations peaked at 2 h and disappeared 7 h after administration. GA was not detected following transdermal administrations, but was following exposure. LSH was not found in the circulatory system after transdermal administration, but TH was. A dose-response correlation was observed for felbinac blood concentration. These findings suggest that zebrafish are capable of absorbing drug molecules through their skin. However, the present data cannot demonstrate that zebrafish is a practical model to predict human skin absorption. Further systemic studies are needed to observe the correlations in percutaneous absorption between humans and zebrafish.
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spelling doaj.art-e5050851df4d46c9bbdde8c736228a2c2023-11-20T12:01:21ZengMDPI AGMolecules1420-30492020-08-012517397410.3390/molecules25173974Evaluation of the Percutaneous Absorption of Drug Molecules in ZebrafishDaizo Morikane0Liqing Zang1Norihiro Nishimura2DIA Pharmaceutical Co., Ltd., Kashihara, Nara 634-0803, JapanGraduate School of Regional Innovation Studies, Mie University, Tsu, Mie 514-8507, JapanGraduate School of Regional Innovation Studies, Mie University, Tsu, Mie 514-8507, JapanIn recent decades, zebrafish (<i>Danio rerio</i>) has become a widely used vertebrate animal model for studying development and human diseases. However, studies on skin medication using zebrafish are rare. Here, we developed a novel protocol for percutaneous absorption of molecules via the zebrafish tail skin, by applying a liquid solution directly, or using a filter paper imbibed with a chemical solution (coating). Human skin is capable of absorbing felbinac and loxoprofen sodium hydrate (LSH), but not glycyrrhetinic acid (GA) and terbinafine hydrochloride (TH). To evaluate the possibility and the quality of transdermal absorption in zebrafish, we transdermally administered these four drugs to zebrafish. Pharmacokinetics showed that felbinac was present in the blood of zebrafish subjected to all administration methods. Felbinac blood concentrations peaked at 2 h and disappeared 7 h after administration. GA was not detected following transdermal administrations, but was following exposure. LSH was not found in the circulatory system after transdermal administration, but TH was. A dose-response correlation was observed for felbinac blood concentration. These findings suggest that zebrafish are capable of absorbing drug molecules through their skin. However, the present data cannot demonstrate that zebrafish is a practical model to predict human skin absorption. Further systemic studies are needed to observe the correlations in percutaneous absorption between humans and zebrafish.https://www.mdpi.com/1420-3049/25/17/3974drug screeningfelbinacglycyrrhetinic acidpharmacokineticszebrafish
spellingShingle Daizo Morikane
Liqing Zang
Norihiro Nishimura
Evaluation of the Percutaneous Absorption of Drug Molecules in Zebrafish
Molecules
drug screening
felbinac
glycyrrhetinic acid
pharmacokinetics
zebrafish
title Evaluation of the Percutaneous Absorption of Drug Molecules in Zebrafish
title_full Evaluation of the Percutaneous Absorption of Drug Molecules in Zebrafish
title_fullStr Evaluation of the Percutaneous Absorption of Drug Molecules in Zebrafish
title_full_unstemmed Evaluation of the Percutaneous Absorption of Drug Molecules in Zebrafish
title_short Evaluation of the Percutaneous Absorption of Drug Molecules in Zebrafish
title_sort evaluation of the percutaneous absorption of drug molecules in zebrafish
topic drug screening
felbinac
glycyrrhetinic acid
pharmacokinetics
zebrafish
url https://www.mdpi.com/1420-3049/25/17/3974
work_keys_str_mv AT daizomorikane evaluationofthepercutaneousabsorptionofdrugmoleculesinzebrafish
AT liqingzang evaluationofthepercutaneousabsorptionofdrugmoleculesinzebrafish
AT norihironishimura evaluationofthepercutaneousabsorptionofdrugmoleculesinzebrafish